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Oxytocin

PubChem CID
439302
Structure
Oxytocin_small.png
Molecular Formula
Synonyms
  • OXYTOCIN
  • 50-56-6
  • Pitocin
  • Endopituitrina
  • Ocytocin
Molecular Weight
1007.2 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-06-24
  • Modify:
    2025-01-11
Description
Oxytocin is a cyclic nonapeptide hormone with amino acid sequence CYIQNCPLG that also acts as a neurotransmitter in the brain; the principal uterine-contracting and milk-ejecting hormone of the posterior pituitary. Together with the neuropeptide vasopressin, it is believed to influence social cognition and behaviour. It has a role as an oxytocic and a vasodilator agent. It is a peptide hormone and a heterodetic cyclic peptide.
Sir Henry H. Dale first identified oxytocin and its uterine contractile properties in 1906. Like all other neurohypophysial hormones, oxytocin is composed of nine amino acids with a disulfide bridge between the Cys 1 and 6 residues. In the mid-1950s, synthetic oxytocin was successfully synthesized by a biochemist named Vincent du Vigneaud; he was later recognized with a Nobel prize for his work. Oxytocin continues to be an important tool in modern obstetrics to induce labor when indicated and to manage postpartum hemorrhage. It is estimated that labor induction with oxytocin is used in almost 10% of deliveries globally. It should be noted that there are risks associated with oxytocin intervention during childbirth. Oxytocin should be used judiciously only when necessary and by experienced healthcare practitioners. Although most commonly linked to labor and delivery, oxytocin actually has broad peripheral and central effects. It plays an important role in pair bonding, social cognition and functioning, and even fear conditioning. Oxytocin also serves a role in metabolic homeostasis and cardiovascular regulation.
Oxytocin has been reported in Oxystelma esculentum with data available.
See also: Oxytocin acetate (active moiety of) ... View More ...

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Oxytocin.png

1.2 3D Status

Conformer generation is disallowed since too many atoms, too flexible

2 Biologic Description

SVG Image
SVG Image
IUPAC Condensed
H-Cys(1)-Tyr-Ile-Gln-Asn-Cys(1)-Pro-Leu-Gly-NH2
Sequence
CYIQNCPLG
PLN
H-C(1)YIQNC(1)PLG-[NH2]
HELM
PEPTIDE1{C.Y.I.Q.N.C.P.L.G.[am]}$PEPTIDE1,PEPTIDE1,1:R3-6:R3$$$
IUPAC
L-cysteinyl-L-tyrosyl-L-isoleucyl-L-glutaminyl-L-asparagyl-L-cysteinyl-L-prolyl-L-leucyl-glycinamide (1->6)-disulfide

3 Names and Identifiers

3.1 Computed Descriptors

3.1.1 IUPAC Name

(2S)-1-[(4R,7S,10S,13S,16S,19R)-19-amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-[(2S)-butan-2-yl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-N-[(2S)-1-[(2-amino-2-oxoethyl)amino]-4-methyl-1-oxopentan-2-yl]pyrrolidine-2-carboxamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

3.1.2 InChI

InChI=1S/C43H66N12O12S2/c1-5-22(4)35-42(66)49-26(12-13-32(45)57)38(62)51-29(17-33(46)58)39(63)53-30(20-69-68-19-25(44)36(60)50-28(40(64)54-35)16-23-8-10-24(56)11-9-23)43(67)55-14-6-7-31(55)41(65)52-27(15-21(2)3)37(61)48-18-34(47)59/h8-11,21-22,25-31,35,56H,5-7,12-20,44H2,1-4H3,(H2,45,57)(H2,46,58)(H2,47,59)(H,48,61)(H,49,66)(H,50,60)(H,51,62)(H,52,65)(H,53,63)(H,54,64)/t22-,25-,26-,27-,28-,29-,30-,31-,35-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.3 InChIKey

XNOPRXBHLZRZKH-DSZYJQQASA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

3.1.4 SMILES

CC[C@H](C)[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N1)CC2=CC=C(C=C2)O)N)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

3.2 Molecular Formula

C43H66N12O12S2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

3.3 Other Identifiers

3.3.1 CAS

50-56-6

3.3.2 European Community (EC) Number

3.3.3 ChEBI ID

3.3.4 ChEMBL ID

3.3.5 DrugBank ID

3.3.6 DSSTox Substance ID

3.3.7 KEGG ID

3.3.8 Metabolomics Workbench ID

3.3.9 NCI Thesaurus Code

3.3.10 Nikkaji Number

3.3.11 PharmGKB ID

3.3.12 Pharos Ligand ID

3.3.13 RXCUI

3.3.14 Wikidata

3.3.15 Wikipedia

3.4 Synonyms

3.4.1 MeSH Entry Terms

  • Ocytocin
  • Oxytocin
  • Pitocin
  • Syntocinon

3.4.2 Depositor-Supplied Synonyms

4 Chemical and Physical Properties

4.1 Computed Properties

Property Name
Molecular Weight
Property Value
1007.2 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
-2.6
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
12
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
15
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
17
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
1006.43645793 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
1006.43645793 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
450 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
69
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
1870
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
9
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

4.2 Experimental Properties

4.2.1 Color / Form

White powder
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-410

4.2.2 Melting Point

4.2.3 Solubility

Soluble in water, butanol
Lide, D.R. CRC Handbook of Chemistry and Physics 88TH Edition 2007-2008. CRC Press, Taylor & Francis, Boca Raton, FL 2007, p. 3-410

4.2.4 Optical Rotation

SPECIFIC OPTICAL ROTATION: -26.2 DEG @ 22 °C/D (0.53 G/100 ML WATER)
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 904

4.2.5 Decomposition

When heated to decomposition it emits toxic fumes of /sulfur oxide/ and /nitric oxide/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2809

4.2.6 Hydrophobicity

-2.7

4.2.7 Isoelectric Point

5.51

4.2.8 Collision Cross Section

303.8 Ų [M+H]+ [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

294.98 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

298.97 Ų [M-H]- [CCS Type: DT; Method: stepped-field]
297.9 Ų [M-H]-
S50 | CCSCOMPEND | The Unified Collision Cross Section (CCS) Compendium | DOI:10.5281/zenodo.2658162

4.2.9 Other Experimental Properties

Shows an activity of 450-500 USP units/mg when compared with USP posterior pituitary reference std
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 904
Oxytocin from beef and hog sources shows no difference in amino acid composition
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 904

4.3 Chemical Classes

4.3.1 Drugs

4.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Oxytocics; Pituitary Hormones, Posterior
Human drug -> Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (OXYTOCIN)
Human drug -> Prescription
Paediatric drug
Uterotonics
4.3.1.2 Animal Drugs
Active Ingredients (Oxytocin) -> FDA Greenbook
Pharmaceuticals -> UK Veterinary Medicines Directorate List
S104 | UKVETMED | UK Veterinary Medicines Directorate's List | DOI:10.5281/zenodo.7802119

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Administration of exogenous oxytocin is indicated in the antepartum period to initiate or improve uterine contractions for vaginal delivery in situations where there is fetal or maternal concern. For example, It may be used to induce labor in cases of Rh sensitization, maternal diabetes, preeclampsia at or near term, and when delivery is indicated due to prematurely ruptured membranes. Importantly, oxytocin is not approved or indicated for elective induction of labor. Oxytocin may be used to reinforce labor in select cases of uterine inertia and as adjunctive therapy in the management of incomplete or inevitable abortion. In the postpartum period, oxytocin may be used to induced contractions in the 3rd stage of labor and to control postpartum bleeding or hemorrhage.
Treatment of Prader-Willi syndrome

7.2 Drug Classes

Breast Feeding; Lactation; Milk, Human; Oxytocics; Pituitary Hormones, Posterior

7.3 WHO Essential Medicines

Drug
Drug Classes
Uterotonics
Formulation
Parenteral - General injections - unspecified: 10 IU per mL
Indication
Postpartum haemorrhage

7.4 FDA Approved Drugs

7.5 FDA Orange Book

7.6 FDA National Drug Code Directory

7.7 FDA Green Book

7.8 Drug Labels

Drug and label
Active ingredient and drug

7.9 Clinical Trials

7.9.1 ClinicalTrials.gov

7.9.2 EU Clinical Trials Register

7.9.3 NIPH Clinical Trials Search of Japan

7.10 EMA Drug Information

Type
Paediatric investigation
Active Substance
Therapeutic Area
Endocrinology-Gynaecology-Fertility-Metabolism
Drug Form
Nasal spray, solution
Administration Route
Nasal use
Decision Type
P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s)
Decision Date
2022-08-11

7.11 Therapeutic Uses

Oxytocin is indicated for the medical rather than the elective induction of labor. Available data and information are inadequate to define the benefits-to-risks considerations in the use of the drug product for elective induction. Elective induction of labor is defined as the initiation of labor for convenience in an individual with a term pregnancy who is free of medical indications. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
Oxytocin is indicated for the initiation or improvement of uterine contractions, where this is desirable and considered suitable for reasons of fetal or maternal concern, in order to achieve early vaginal delivery. It is indicated for induction of labor in patients with a medical indication for the initiation of labor, such as Rh problems, maternal diabetes, preeclampsia at or near term, when delivery is in the best interests of mother and fetus or when membranes are prematurely ruptured and delivery is indicated... /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
Oxytocin is indicated for stimulation or reinforcement of labor, as in selected cases of uterine inertia... /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
Oxytocin is indicated as adjunctive therapy in the management of incomplete or inevitable abortion. In the first trimester, curettage is generally considered primary therapy. In second trimester abortion, oxytocin infusion will often be successful in emptying the uterus. Other means of therapy, however, may be required in such cases. /Included in US product label/
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
For more Therapeutic Uses (Complete) data for Oxytocin (11 total), please visit the HSDB record page.

7.12 Drug Warnings

When oxytocin is administered in excessive dosage, with abortifacients or to sensitive patients, hyperstimulation of the uterus, with strong (hypertonic) and/or prolonged (tetanic) contractions, or a resting uterine tone of 15-20 mm H2O between contractions may occur, possibly resulting in uterine rupture, cervical and vaginal lacerations, postpartum hemorrhage, abruptio placentae, impaired uterine blood flow, amniotic fluid embolism, and fetal trauma including intracranial hemorrhage.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Increased uterine motility may cause adverse fetal effects, including sinus bradycardia, tachycardia, premature ventricular complexes and other arrhythmias, permanent CNS or brain damage, and death secondary to asphyxia. Excessive maternal dosage or administration of the drug to sensitive women also can cause uteroplacental hypoperfusion and variable deceleration of fetal heart rate, fetal hypoxia, perinatal hepatic necrosis, and fetal hypercapnia. Rare incidents of pelvic hematoma have been reported, but these were probably also related to the high incidence of operative vaginal deliveries in primiparas, the fragility of engorged pelvic veins (especially if varicosed), and faulty episiotomy repair.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
When large amounts of oxytocin are administered, severe decreases in maternal systolic and diastolic blood pressure, increases in heart rate, systemic venous return and cardiac output, and arrhythmia may occur; these effects may be particularly hazardous to patients with valvular heart disease and those receiving spinal and epidural anesthesia.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Postpartum bleeding may be increased by administration of oxytocin; this effect may be related to reports of oxytocin-induced thrombocytopenia, afibrinogenemia, and hypoprothrombinemia. By carefully controlling delivery, the incidence of postpartum bleeding may be minimized.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
For more Drug Warnings (Complete) data for Oxytocin (22 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Oxytocin is a nonapeptide, pleiotropic hormone that exerts important physiological effects. It is most well known to stimulate parturition and lactation, but also has important physiological influences on metabolic and cardiovascular functions, sexual and maternal behaviour, pair bonding, social cognition, and fear conditioning. It is worth noting that oxytocin receptors are not limited to the reproductive system but can be found in many peripheral tissues and in central nervous system structures including the brain stem and amygdala.

8.2 MeSH Pharmacological Classification

Oxytocics
Drugs that stimulate contraction of the myometrium. They are used to induce LABOR, OBSTETRIC at term, to prevent or control postpartum or postabortion hemorrhage, and to assess fetal status in high risk pregnancies. They may also be used alone or with other drugs to induce abortions (ABORTIFACIENTS). Oxytocics used clinically include the neurohypophyseal hormone OXYTOCIN and certain prostaglandins and ergot alkaloids. (From AMA Drug Evaluations, 1994, p1157) (See all compounds classified as Oxytocics.)

8.3 FDA Pharmacological Classification

Non-Proprietary Name
OXYTOCIN
Pharmacological Classes
Oxytocin [CS]; Oxytocic [EPC]; Increased Uterine Smooth Muscle Contraction or Tone [PE]

8.4 ATC Code

H - Systemic hormonal preparations, excl. sex hormones and insulins

H01 - Pituitary and hypothalamic hormones and analogues

H01B - Posterior pituitary lobe hormones

H01BB - Oxytocin and analogues

H01BB02 - Oxytocin

H01BB02

8.5 Absorption, Distribution and Excretion

Absorption
Oxytocin is administered parenterally and is fully bioavailable. It takes approximately 40 minutes for oxytocin to reach steady-state concentrations in the plasma after parenteral administration.
Route of Elimination
The enzyme oxytocinase is largely responsible for the metabolism and regulation of oxytocin levels in pregnancy; only a small percentage of the neurohormone is excreted in the urine unchanged.
Clearance
In a study that observed 10 women who were given oxytocin to induce labor, the mean metabolic clearance rate was 7.87 mL/min.
Oxytocin is destroyed by chymotrypsin in the GI tract. Uterine response occurs almost immediately and subsides within 1 hour following iv administration of oxytocin. Following im injection of the drug, uterine response occurs within 3-5 minutes and persists for 2-3 hours. Following intranasal application of 10-20 units of oxytocin (nasal preparations are no longer commercially available in the US), contractions of myoepithelial tissue surrounding the alveoli of the breasts begin within a few minutes and continue for 20 minutes; iv oxytocin produces the same effect with a dose of 100-200 milliunits.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349
Like vasopressin, oxytocin is distributed throughout the extracellular fluid. Small amounts of oxytocin probably reach the fetal circulation.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349
It is not known whether this drug is excreted in human milk.
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
Its rapid removal from plasma is accomplished largely by the kidney and the liver. Only small amounts oxytocin are excreted in the urine unchanged.
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
For more Absorption, Distribution and Excretion (Complete) data for Oxytocin (7 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Oxytocin is rapidly removed from the plasma by the liver and kidney. The enzyme oxytocinase is largely responsible for the metabolism and regulation of oxytocin levels in pregnancy and only a small percentage of the neurohormone is excreted in the urine unchanged. Oxytocinase activity increases throughout pregnancy and peaks in the plasma, placenta and uterus near term. The placenta is a key source of oxytocinase during gestation and produces increasing amounts of the enzyme in response to increasing levels of oxytocin produced by the mother. Oxytocinase activity is also expressed in mammary glands, heart, kidney, and the small intestine. Lower levels of activity can be found in the brain, spleen, liver, skeletal muscle, testes, and colon. The level of oxytocin degradation is negligible in non-pregnant women, men, and cord blood.
Oxytocinase, a circulating enzyme produced early in pregnancy, is also capable of inactivating the polypeptide.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349
During pregnancy ... "oxytocinase" ... is capable of inactivating oxytocin by cleavage of the 1-cysteine to 2-tyrosine peptide bond.
Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 938

8.7 Biological Half-Life

The plasma half-life of oxytocin ranges from 1-6 minutes. The half-life is decreased in late pregnancy and during lactation.
Oxytocin has a plasma half-life of about 3 to 5 minutes.
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243

8.8 Mechanism of Action

Oxytocin plays a vital role in labour and delivery. The hormone is produced in the hypothalamus and is secreted from the paraventricular nucleus to the posterior pituitary where it is stored. It is then released in pulses during childbirth to induce uterine contractions. The concentration of oxytocin receptors on the myometrium increases significantly during pregnancy and reaches a peak in early labor. Activation of oxytocin receptors on the myometrium triggers a downstream cascade that leads to increased intracellular calcium in uterine myofibrils which strengthens and increases the frequency of uterine contractions. In humans, most hormones are regulated by negative feedback; however, oxytocin is one of the few that is regulated by positive feedback. The head of the fetus pushing on the cervix signals the release of oxytocin from the posterior pituitary of the mother. Oxytocin then travels to the uterus where it stimulates uterine contractions. The elicited uterine contractions will then stimulate the release of increasing amounts of oxytocin. This positive feedback loop will continue until parturition. Since exogenously administered and endogenously secreted oxytocin result in the same effects on the female reproductive system, synthetic oxytocin may be used in specific instances during the antepartum and postpartum period to induce or improve uterine contractions.
The pharmacologic and clinical properties of oxytocin are identical with those of naturally occurring oxytocin principle of the posterior lobe of pituitary. Oxytocin exerts a selective action on the smooth musculature of the uterus, particularly toward the end of pregnancy, during labor, and immediately following delivery. Oxytocin stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions, and raises the tone of the uterine musculature.
US Natl Inst Health; DailyMed. Current Medication Information for Oxytocin injection (June 2009). Available from, as of February 10, 2010: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10243
Oxytocin indirectly stimulates contraction of uterine smooth muscle by increasing the sodium permeability of uterine myofibrils. High estrogen concentrations lower the threshold for uterine response to oxytocin. Uterine response to oxytocin increases with the duration of pregnancy and is greater in patients who are in labor than those not in labor; only very large doses elicit contractions in early pregnancy. Contractions produced in the term uterus by oxytocin are similar to those occurring during spontaneous labor. In the term uterus, oxytocin increases the amplitude and frequency of uterine contractions which in turn tend to decrease cervical activity producing dilation and effacement of the cervix and to transiently impede uterine blood flow.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Oxytocin contracts myoepithelial cells surrounding the alveoli of the breasts, forcing milk from the alveoli into the larger ducts and thus facilitating milk ejection. The drug possesses no galactopoietic properties.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Oxytocin produces vasodilation of vascular smooth muscle, increasing renal, coronary, and cerebral blood flow. Blood pressure is usually unchanged, but following iv administration of very large doses or undiluted solutions, blood pressure may decrease transiently, and tachycardia and an increase in cardiac output may be reflexly induced. Any initial fall in blood pressure is usually followed by a small but sustained increase in blood pressure. In contrast to vasopressin, oxytocin has minimal antidiuretic effects; however, water intoxication may occur when oxytocin is administered with an excessive volume of electrolyte-free iv fluids and/or at too rapid a rate.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349
For more Mechanism of Action (Complete) data for Oxytocin (15 total), please visit the HSDB record page.

9 Use and Manufacturing

9.1 Uses

MEDICATION
MEDICATION (Vet)

9.1.1 Use Classification

Human Drugs -> EU pediatric investigation plans
Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9.2 Methods of Manufacturing

Obtained from the posterior lobe of the pituitary of healthy hogs or cattle.
R. Hendrickson, et al. (eds.); Remington: The Science and Practice of Pharmacy 21th ed. Lippincott Williams and Wilkins, Baltimore, Maryalnd, p.1433 (2005)

9.3 Formulations / Preparations

Oxytocin injection, USP ... contains 10 USP units per mL and may be administered iv or im. All commercial preparations are now synthetic.
Gilman, A. G., L. S. Goodman, and A. Gilman. (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 6th ed. New York: Macmillan Publishing Co., Inc. 1980., p. 938
... injection, USP
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 938

9.4 General Manufacturing Information

Each mL of posterior pituitary injection NF possesses oxytocic activity equivalent to 10 USP posterior pituitary units (permissible range, 8.5-12 units) ... /Posterior pituitary/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 566
The hypotensive response of the chicken is the basis for the USP bioassay for oxytocin.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 869

10 Identification

10.1 Analytic Laboratory Methods

Analyte: oxytocin; matrix: chemical identification; procedure: retention time of the peak in the liquid chromatogram with comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.3185 (2008)
Analyte: oxytocin; matrix: chemical purity; procedure: liquid chromatography with ultraviolet detection at 220 nm and comparison to standards
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.3185 (2008)
Analyte: oxytocin; matrix: pharmaceutical preparation (injection solution; nasal solution); procedure: liquid chromatography with ultraviolet detection at 220 nm and comparison to standards (chemical purity)
U.S. Pharmacopeia. The United States Pharmacopeia, USP 32/The National Formulary, NF 27; Rockville, MD: U.S. Pharmacopeial Convention, Inc., p.3186 (2008)
USE OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY IN THE QUALITY CONTROL OF OXYTOCIN.
KRUMMEN K ET AL; USE OF HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) IN THE QUALITY CONTROL OF OXYTOCIN; PHARM TECHNOL 3(9) 77 (1979)
ANALYSIS OF OXYTOCIN IN PHARMACEUTICAL DOSAGE FORMS OR IN SYNTHETIC & NATURAL PRODUCTS BY GRADIENT ELUTION HIGH-PRESSURE LIQUID CHROMATOGRAPHY.
BIEMOND ME F ET AL; QUANTITATIVE DETERMINATION OF POLYPEPTIDES BY GRADIENT ELUTION HIGH-PRESSURE LIQUID CHROMATOGRAPHY; J LIQ CHROMATOGR 2(9) 1407 (1979)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Note
This chemical does not meet GHS hazard criteria for 79.6% (39 of 49) of all reports. Pictograms displayed are for 20.4% (10 of 49) of reports that indicate hazard statements.
Pictogram(s)
Irritant
Health Hazard
Signal
Warning
GHS Hazard Statements

H302 (10.2%): Harmful if swallowed [Warning Acute toxicity, oral]

H361 (14.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

Precautionary Statement Codes

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 49 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 39 of 49 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 9 notifications provided by 10 of 49 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Acute Tox. 4 (10.2%)

Repr. 2 (14.3%)

11.1.3 Skin, Eye, and Respiratory Irritations

May cause irritation. Avoid contact. Avoid inhalation. Remove to fresh air.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)

11.2 Fire Fighting

11.2.1 Fire Fighting Procedures

Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)
As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)

11.3 Accidental Release Measures

11.3.1 Cleanup Methods

Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)

11.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

11.3.3 Preventive Measures

This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)
As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)
/Use/ safety goggles or glasses /and/ protect exposed skin.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)

11.4 Handling and Storage

11.4.1 Storage Conditions

Store in tight container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)
Oxytocin injection should be stored at temperatures less than 15-25 °C but should not be frozen. Pitocin should be refrigerated at 2-8 °C but may be exposed to temperatures ranging from 15-25 °C for up to 30 days; Pitocin exposed to this latter temperature range for longer periods should be discarded.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349

11.5 Exposure Control and Personal Protection

11.5.1 Personal Protective Equipment (PPE)

Engineering controls such as exhaust ventilation are recommended.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)
Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.
United States Pharmacopeial Convention, Inc (USP); MSDS Database Online; Material Safety Data Sheet: Oxytocin; Catalog Number: 1491300; (Revision Date: December 4, 2006)

11.6 Stability and Reactivity

11.6.1 Hazardous Reactivities and Incompatibilities

Oxytocin injection appears to be compatible with most iv infusion fluids but is reported to be physically incompatible with fibrinolysin, norepinephrine bitartrate, prochlorperazine edisylate, and warfarin sodium. Oxytocin injection has also been reported to be incompatible with various other drugs, but the compatibility depends on several factors (eg, the concentration of the drugs, resulting pH, temperature). Specialized references should be consulted for more specific compatibility information.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3349

11.7 Regulatory Information

New Zealand EPA Inventory of Chemical Status
Oxytocin: Does not have an individual approval but may be used under an appropriate group standard

11.7.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including oxytocin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 10, 2010: https://www.accessdata.fda.gov/scripts/cder/ob/docs/queryai.cfm
The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Oxytocin is included on this list.
US FDA/Center for Veterinary Medicine; The Green Book - On Line, Active Ingredients. Oxytocin (50-56-6). Available from, as of March 10, 2010: https://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/default.htm
Oxytocin may be used as a uterine contractor to precipitate and accelerate normal parturition and postpartum evacuation of uterine debris. In surgery it may be used postoperatively following cesarean section to facilitate involution and resistance to the large inflow of blood. It will contract smooth muscle cells of the mammary gland for milk letdown if the udder is in proper physiological state. ... Federal law restricts this drug to use by or on the order of a licensed veterinarian.
21 CFR 522.1680 (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 10, 2010: https://www.ecfr.gov

11.8 Other Safety Information

Chemical Assessment

IMAP assessments - Oxytocin: Human health tier I assessment

IMAP assessments - Oxytocin: Environment tier I assessment

12 Toxicity

12.1 Toxicological Information

12.1.1 Drug Induced Liver Injury

Compound
oxytocin
DILI Annotation
No-DILI-Concern
Label Section
No match
References

M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007

M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015

12.1.2 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Oxytocin is an essential lactation hormone released during breastfeeding that causes milk ejection and appears to have calming effect on the mother. Administration of exogenous oxytocin to mothers having difficulty in breastfeeding has not been clearly shown to have a beneficial effect on lactation success or in the treatment of breast engorgement. It might be of benefit with spinal cord injury where the neuronal connection between the breast and hypothalamus have been lost. Effects on the infant are unlikely when oxytocin is given during breastfeeding.

Some studies suggest that oxytocin given during labor can negatively affect breastfeeding, possibly by reducing sucking behavior in the newborn in a dose-dependent manner, or by decreasing postpartum oxytocin release although study timing of oxytocin administration and study methodology has varied considerably. Another study found no relationship between cumulative oxytocin dosage and breastfeeding success at 1 week postpartum. The effect on breastfeeding might be most important during the initiation of breastfeeding, but may not persist after lactation is established. Two studies found that only oxytocin in conjunction with epidural analgesia reduced breastfeeding, but not oxytocin alone. Another study found that all rhythmic reflexes, the antigravity reflex, and total primitive neonatal reflexes were inhibited by intrapartum oxytocin administration, unrelated to dose, which could adversely affect breastfeeding. Another small study found that exogenous oxytocin for induction or augmentation of labor was positively associated with higher quality of observed mother-infant bonding. Some evidence exists that peripartum oxytocin administration might increase the risk of postpartum depression.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Nasal spray. Intranasal oxytocin is reportedly used by some midwives in Switzerland as a galactogogue. It has been used as part of regimens used by adoptive mothers who wish to breastfeed.

A small study found no difference in symptoms between subcutaneous oxytocin 2.5 international units daily and placebo after 3 days of treatment for breast engorgement.

An early randomized, placebo-controlled trial used oxytocin nasal spray in the mothers of newborns, but lactation management fell far short of what is considered acceptable nowadays. The study found that the spray might be useful in decreasing breast engorgement slightly in the mothers of full-term infants, but no difference was found in the average infant weight loss between birth and day 4 in the oxytocin and placebo groups.

Two similarly designed trials studied oxytocin nasal spray in mothers of preterm newborns who were pumping milk for their infants. The first studied mothers of infants born before 38 weeks and used a total of 3 units of intranasal oxytocin (Syntocinon-Sandoz, 40 units/mL) before pumping each breast for10 minutes a breast pump four times daily. Among primiparous mothers, milk production during days 2 to 5 days postpartum was 1964 mL in those who used oxytocin and 510 mL in those who received placebo spray. Because of the large and statistically significant effect of oxytocin among primiparous women, the trial was stopped after only 8 primiparous mothers had been studied. No statistically significant difference was found between oxytocin and placebo among 4 multiparous women who were attempting to breastfeed for the first time. The paper did not report giving the mothers any instructions in lactation technique.

Fifty-one mothers who delivered an infant of less than 35 weeks gestation were studied. Twenty-seven mothers used 4 units of intranasal oxytocin (Syntocinon-Novartis, 40 units/mL), and 24 mothers received an identical placebo spray before pumping with a breast pump. All mothers were given instructions on using hand massage before pumping and advised to pump every 3 hours. No difference in milk production over the first 5 days postpartum was found between mothers who received oxytocin (median 667 mL) and placebo (median 530 mL), although women receiving oxytocin produced slightly more milk on day 2 of the study. Parity had no effect in this study.

Several factors might explain the differences in findings between the studies. Because of the great interpatient variability in milk production documented in the recent study and the small number of patients in the first study, the finding in the earlier study may have been due to chance. A 50% higher dose of oxytocin was used in the first study, which may have caused a greater effect. Another plausible explanation is the good lactation support given to mothers in the recent larger study that seemed to be lacking in the early study.

Two case reports indicate that oxytocin nasal spray may facilitate letdown in tetraplegic women who have lost the neuronal connection between the nipple and the hypothalamus.

During labor. A study of mothers who received oxytocin during labor found that on the second day postpartum, oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively. Oxytocin infusion also increased serum prolactin.

Logistic regression of data from 585 mothers who had epidural analgesia during labor found that mothers who had received exogenous oxytocin had a 3.3 times greater risk of delayed onset of lactation than women who did not.

An observational study of 20 primiparous women found that those who were exclusively breastfeeding at 3 months (63%) had received a lower dose of oxytocin during labor (mean total dosage 1363 milliunits) than those who were not exclusively breastfeeding (mean total dosage 3088 milliunits). This result was attributed to an inhibitory effect on neonatal sucking by the infant caused by oxytocin.

A small, nonrandomized cohort study found that the newborn infants whose mothers received synthetic oxytocin to induce or maintain labor had a decreased level of prefeeding organization one hour after birth.

A retrospective cohort study in Spain compared breastfeeding outcomes between mothers who received oxytocin during labor (n = 189) and mothers who did not, including those who delivered via elective Cesarean section (n = 127). Mothers who received oxytocin during the first and second stages of labor had a 45% increased risk of bottle feeding and a 129% increased risk of breastfeeding discontinuation by 3 months of age. Effects were most pronounced in women under 27 years of age.

A small prospective study in California compared women who received an epidural infusion of fentanyl and ropivacaine to mothers who did not receive an epidermal during labor. All mothers had normal vaginal deliveries and their infants had 1 uninterrupted hour of skin-to-skin contact immediately postpartum. The study found inverse relationships between the amount of fentanyl and the amount of oxytocin received during labor and the time of the first suckling. Because women who received more fentanyl also tended to receive more oxytocin, the study could not clearly separate the effects of the two drugs.

A small prospective cohort study in Spain followed mothers by telephone postpartum to determine their breastfeeding status. Mothers who had received oxytocin during labor were breastfeeding at a similar rate as those who had not at 1, 3 and 6 months postpartum.

A nonblinded, nonrandomized study compared breastfeeding among the infants of mothers who received oxytocin during delivery (n = 70) and those who did not (n = 90) in two Iranian hospitals. Mothers were primiparous and infants were full term. Infant breastfeeding behavior was assessed to be either successful or unsuccessful within 2 hours of delivery. Infants whose mothers received oxytocin were judged to successfully breastfeed 48.6% compared to 82.2% among the infants of mothers who did not receive oxytocin. Use of opiate pain relievers in the two groups was not stated.

A retrospective cohort study compared breastfeeding results between women who did and did not receive oxytocin during labor. After correcting for confounding factors, the study found that exogenous oxytocin impaired breastfeeding during the first hour postpartum, but not at 3 months postpartum. High pregestational body mass index was the best predictor of an impaired third month's postpartum breastfeeding.

A retrospective case-control study conducted in two hospitals in central Iran compared breastfeeding behaviors in the first 2 hours postdelivery by infants of 4 groups of primiparous women with healthy, full-term singleton births who had vaginal deliveries. The groups were those who received no medications during labor, those who received oxytocin plus scopolamine, those who received oxytocin plus meperidine, and those who received oxytocin, scopolamine and meperidine. The infants in the no medication group performed better than those in all other groups, and the oxytocin plus scopolamine group performed better than the groups that had received meperidine.

A prospective cohort study in Spain found no relationship between oxytocin dose during labor or postpartum with the duration of breastfeeding. However, elective cesarean section without oxytocin resulted in the greatest risk of stopping exclusive breastfeeding.

An observational study in Sweden compared nursing behaviors of the infants of mothers who received intravenous oxytocin or intramuscular oxytocin with or without receiving epidural analgesia with sufentanil and bupivacaine. Infants of mothers who received oxytocin infusions alone during labor breastfed as well as those of mothers who had no interventions during labor. Mothers who received oxytocin plus epidural analgesia had reduced breastfeeding behaviors and more weight loss at 2 days postpartum than those who did not receive epidural analgesia. The mothers of infants who breastfed well had greater variability in serum oxytocin than those whose infants did not breastfeed well.

A study examined the effects of low, medium and high doses of intrapartum synthetic oxytocin administered to mothers who received no oxytocin. A dose-related decrease in several infant breastfeeding behaviors and the number of exclusive nursing bouts at 24, 48 and 72 hours was found, but there was no difference in the rate of exclusive breastfeeding at 3 months postpartum.

In a study of primiparous women with an uncomplicated pregnancy, women were given oxytocin 1 to 2 milliunits/min initially, with dosage increases of 1 to 2 milliunits/min every 30 minutes until effective contractions were achieved, up to a maximum of 20 milliunits/min. Some women received epidural analgesia with ropivacaine and fentanyl, some received oxytocin alone and other received neither. Breastfeeding outcomes in the three groups were compared at 3 days, 1 month and 4 months postpartum. The study found no relationship between this low-dose oxytocin use and breastfeeding success, but that epidermal analgesia reduced maternal salivary oxytocin levels, lowered milk supply at 3 days and 1 month postpartum, and decreased rates of breastfeeding at 4 months postpartum.

A case-control study in a hospital in Istanbul, Türkiye compared 44 women who received oxytocin for induction of labor to 44 women who did not. There was no significant difference between the mean scores of the Breastfeeding Self-Efficacy Scale and the LATCH scores between the two groups.

A multicenter study in Sweden compared breastfeeding outcomes of 1395 women who received oxytocin during labor. After adjusting for confounding variables (maternal age, early pregnancy BMI, epidural analgesia, and infant weight >4 kg), no difference was found in the breastfeeding rates at 1 week postpartum over the range of cumulative oxytocin dosages that the mothers received.

The sucking ability of 29 vaginally delivered infants whose mothers received oxytocin during delivery were compared to 35 infants whose mothers received no oxytocin. The average maternal oxytocin dose was 3.45 IU over an average of 354 minutes. The infants in the oxytocin group had fewer sucking bursts, longer times between bursts and more variability in sucking than those not exposed. At 1 month postpartum, infants exposed to oxytocin were less likely to be exclusively breastfed than those not exposed (17% vs 43%). The authors concluded that infant sucking ability was impaired for up to 48 hours after maternal oxytocin infusion during labor.

12.1.3 Acute Effects

12.1.4 Interactions

Severe hypertension has been reported when oxytocin was given 3-4 hours following prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Cyclopropane anesthesia may modify oxytocin's cardiovascular effects, producing less pronounced tachycardia but more severe hypotension than occurs with oxytocin alone; maternal sinus bradycardia with abnormal atrioventricular rhythms has been noted when oxytocin was used concomitantly with cyclopropane anesthesia.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348
Oxytocin reportedly has delayed induction of thiopental anesthesia by producing venous spasm that caused peripheral pooling of thiopental; however, this interaction has not been conclusively established.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 3348

12.1.5 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3Rd edition, Elsevier Mosby, St. Louis, MO 2005, p. 160-1

12.1.6 Human Toxicity Excerpts

/HUMAN EXPOSURE STUDIES/ ... Thirty-eight healthy women scheduled for a surgical suction curettage with general anesthesia were enrolled /in this study/ to assess the effect of oxytocin on QT interval. General anesthesia was induced by propofol and maintained by either propofol (n = 18) or sevoflurane (n = 20). Electrocardiographic recordings were obtained before and at 1, 2, 3, and 5 minutes after a 10-U intravenous bolus of oxytocin. Intravenous oxytocin induced a pronounced QTc interval prolongation of 41 +/- 21 ms ( P < 0.0001), which was maximal 1 minute after administration. The QTc interval returned to control values 3 minutes after oxytocin bolus. Oxytocin bolus also induced an increase in heart rate of 19 +/- 10 beats/min and a significant decrease in systolic arterial pressure of 11 +/- 9 mm Hg (both P < 0.0001). The drug used to maintain anesthesia was not an independent factor of QT interval prolongation in ANOVA analysis. Oxytocin intravenous bolus induced a large and transient QTc interval prolongation, suggesting that it may lead to proarrhythmia in circumstances favoring QTc interval increase.
Charbit B et al; Clin Pharmacol Ther 76 (4): 359-64 (2004).
/HUMAN EXPOSURE STUDIES/ ... In humans, oxytocin has been found to enhance trust and the ability to interpret the emotions of others. It has been suggested that oxytocin may enhance facial processing by increasing focus on the eye region of human faces. In a double-blind, randomized, placebo-controlled, between-subject design, /investigators/ tracked the eye movements of 52 healthy male volunteers who were presented with 24 neutral human faces after intranasal administration of 24 IU oxytocin or placebo. Participants given oxytocin showed an increased number of fixations and total gaze time toward the eye region compared with placebo participants. Oxytocin increases gaze specifically toward the eye region of human faces. This may be one mechanism by which oxytocin enhances emotion recognition, interpersonal communication, and social approach behavior in humans. Findings suggest a possible role for oxytocin in the treatment of disorders characterized by eye-gaze avoidance and facial processing deficits.
Guastella AJ et al; Biol Psychiatry 63 (1): 3-5 (2008).
/HUMAN EXPOSURE STUDIES/ The aim of the work was to compare labor courses, ways of delivery, condition of the newborns in spontaneous and oxytocin-related labors and to analyse the indications for oxytocin administration. 2198 full-term deliveries (pregnant women qualified for elective caesarean section were excluded from the study) at the Provincial Hospital in Przemys'l, Poland. Labors with the adjunctive oxytocin infusion--1102 women. Spontaneous labors (without oxytocin administration)--1096 women. The analysis of the compatibility of measured traits was carried out by the Chi-squared test (Chi2), p < 0.05 was assumed as statistically significant level. Indications for the oxytocin administration: secondary hypokinetic contractions of the uterus (642 labors--58.25%), premature rupture of membranes (176 labors - 15.97 %). Deliveries by caesarean section: 1. study group--187 women (16.97%). 2. control group--97 women (8.85%). Chi2 = 32.192; df = 1; p = 0.0000. Newborns after vaginal labors scored 7 or below according to the Apgar in the first minute after the delivery. 1. study group--35 newborns (8.7%); 2. control group--18 newborns (1.8%) Chi2 = 5.493; df = 1; p = 0.0190. Newborns hospitalized for over 48 hours: 1. study group--346 (31.39%); 2. control group--216 newborns (19.70%). Chi2 = 39.454; df = 1; p = 0.0000. Hypokinetic uterine contractions were the most frequent indication for oxytocin administration during labor. Oxytocin administration increases twice the risk of delivery by the caesarean section. Newborns after vaginal oxytocin-related labours scored 7 or below on the Apgar score in the first minute after the birth when compared to the newborns after spontaneous labor. Oxytocin administration during parturition elongates the time of newborns hospitalization.
Raba G, Baran P; Ginekol Pol 80 (7): 508-11 (2009).
/HUMAN EXPOSURE STUDIES/ Oxytocin (OT) effect on ghrelin-stimulated neuropeptide Y (NPY) secretion was evaluated in 12 normal men. Tests: ghrelin (1 ug/kg B.W. as an intravenous bolus); OT (2 mIU/min infusion); ghrelin plus OT; normal saline. Plasma NPY did not change during saline or OT infusions, whereas it showed a significant 29% increase vs baseline at 15 min after ghrelin injection. When OT was present, ghrelin-induced NPY increment was completely abolished. Results show that oxytocin modulates the NPY response to ghrelin, whereas it is unable to produce direct inhibitions of basal circulating NPY levels.
Coiro V et al; J Neural Transm 115 (9): 1265-7 (2008).
For more Human Toxicity Excerpts (Complete) data for Oxytocin (21 total), please visit the HSDB record page.

12.1.7 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The effects of oxytocin on fetal and placental growth and on maternal weight gain and accumulation of body fat were studied in ad libitum-fed and food-restricted (receiving 70% of the food intake of the ad libitum-fed group) pregnant rats. Further, a possible role of the IGF axis in mediating oxytocin-induced changes was assessed. Pregnant rats were injected subcutaneously once a day during gestational d 1-5 with saline or oxytocin (1 mg/kg). Ad libitum-fed oxytocin-treated pregnant rats had higher circulating levels of IGF-I, larger placentas, fetuses, and newborn pups and contained less body fat at the end of pregnancy. In food-restricted dams, oxytocin-treatment had no effect on fetal and placental growth. Additionally, food restriction attenuated the normal increase in IGF binding protein-3 protease proteolysis during pregnancy. The results show that oxytocin may affect maternal adaptations to pregnancy and stimulate fetal growth. /The authors/ suggest that this effect may be mediated by increased IGF-I in ad libitum-fed animals, whereas food restriction may block this effect by resulting in low levels of circulating IGF-I and by attenuating the pregnancy-associated increase in IGF binding protein-3 protease activity and, thereby, further compromise IGF bioavailability.
Sohlstrom A et al; Pediatr Res 46 (3): 339-44 (1999).
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ ... Ten pregnant ewes received either saline solution (control, n = 5) or long-term administration of oxytocin (600 microU. kg-1. min-1) in 5-minute pulses every 20 minutes to the maternal jugular vein beginning at 96 days' gestation (n = 5). Maternal tracheal tubes, fetal carotid artery and jugular vein catheters, and electrocorticographic and electromyographic electrodes were placed with the animals under halothane general anesthesia at 122 days' gestation. At 131 days' gestation fetal hypoxemia was induced for 1 hour. Maternal and fetal arterial blood gas samples were obtained at 60, 15, and 5 minutes before the start of hypoxemia and at 5, 10, 20, 30, 40, 60, and 120 minutes after the start of hypoxemia. Baseline PO2 before hypoxemia was significantly lower and oxygen content was significantly higher in fetuses in the long-term oxytocin group than in control fetuses. At the end of hypoxemia the fetal pH, oxygen saturation, and oxygen content were significantly higher in the long-term oxytocin group than in the control group, although PO2 did not differ between groups. The fetal blood oxygen dissociation curve was shifted to the left in the long-term oxytocin group. During hypoxemia the absolute fetal blood pH was higher and the blood pH variation was lower in long-term oxytocin group than in the control group. Lower baseline and hypoxia-induced fetal plasma cortisol concentrations were observed in fetuses in the long-term oxytocin group than in fetuses of control ewes. Increased contracture frequency during a period of 35 days shifts the fetal oxygen dissociation curve toward the left and alters fetal response to acute hypoxemia.
Shinozuka N et al; Am J Obstet Gynecol 180 (5): 1202-8 (1999).
/OTHER TOXICITY INFORMATION/ The objective was to characterize the urinary oxytocin (OT) system with the goal of using it as a biomarker for neurohypophyseal peptide secretion. We studied urinary OT secretion in mice under three conditions: (1) in OT gene deletion mice (OT -/-) which lack the ability to produce the peptide; (2) after arterial vascular infusion of OT and (3) after physiological stimulation with consumption of 2% sodium chloride. OT was measured by radioimmunoassay (RIA) and Surface-Enhanced Laser Desorption Ionization Time of Flight Mass Spectroscopy (SELDI TOF MS). In OT -/- mice (n=25), urinary OT levels were not detectable, while in OT +/+ mice (n=23) levels were 250.2+/-35.3 pg/mL. To evaluate blood/urine transfer, mice with chronic carotid arterial catheters were infused with saline or OT (5 or 20 pmol/min). Peak urine OT levels were 89+/-11.5 and 844+/-181 ng/mL in the low and high OT groups, respectively. Proteomic evaluation showed MS peaks, corresponding to OT ( approximately 1009 Da) and a related peptide ( approximately 1030 Da) with highest levels in mice infused with OT. Salt loading (5 days of 2% NaCl as drinking water) increased plasma osmolality (3.3%), increased plasma and urinary vasopressin (AVP), but caused no changes in OT. Thus, using non-invasive urine samples, we document that urinary OT and AVP can be used to monitor changes in peptide secretion. Urinary OT and AVP, as well as other urinary peptides, may provide a viable biomarker for peptide secretion and may be useful in clinical studies.
Polito AB et al; Peptides. 2006 Nov;27(11):2877-84 (2006).

12.2 Ecological Information

12.2.1 Natural Pollution Sources

A hormone secreted by the posterior lobe of the pituitary gland. Its chief action is stimulation of the contraction of the smooth muscle of the uterus. It contains eight different amino acids.
Lewis, R.J. Sr.; Hawley's Condensed Chemical Dictionary 15th Edition. John Wiley & Sons, Inc. New York, NY 2007., p. 938

12.2.2 Milk Concentrations

Samples of human milk obtained from lactating women in the early postpartum period were assayed for oxytocin concentrations by specific RIA, following extraction procedures with Florisil. Mean oxytocin concentrations in human milk at postpartum day 1 to 5 were 4.5 +/- 1.1, 4.7 +/- 1.1, 4.0 +/- 1.3, 3.2 +/- 0.4, 3.3 +/- 0.6 microunits/mL (+/- SE), respectively. Oxytocin levels in milk were significantly increased by nursing (3.1 +/- 0.6, 5.3 +/- 1.0 microunits/mL, respectively). 3H-oxytocin in human milk was stable even after incubation at 37 degrees C for 2 hours. The dilution curve for milk was parallel to the curve for the standard oxytocin. The chromatographic fraction of immunoreactive oxytocin was identical to that of 3H-oxytocin. 3H-oxytocin was administered to lactating rats. Radioactivity in the neonatal gastric contents and plasma were 12.8% and 4.4% of the counts in the maternal plasma. It was made clear that oxytocin is stable in milk and that oxytocin in maternal blood can be transferred to milk and then to neonates.
Takeda S et al; Endocrinol Jpn 33 (6): 821-6 (1986).

12.2.3 Probable Routes of Human Exposure

NIOSH (NOES Survey 1981-1983) has statistically estimated that 2,515 workers (1,568 of these were female) were potentially exposed to oxytocin in the US(1).
(1) NIOSH; NOES. National Occupational Exposure Survey conducted from 1981-1983. Estimated numbers of employees potentially exposed to specific agents by 2-digit standard industrial classification (SIC). Available from as of Jan 4, 2010: https://www.cdc.gov/noes/

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Wiley References

14.6 Nature Journal References

14.7 Chemical Co-Occurrences in Literature

14.8 Chemical-Gene Co-Occurrences in Literature

14.9 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 Chemical Co-Occurrences in Patents

15.4 Chemical-Disease Co-Occurrences in Patents

15.5 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: Metabolite

19.5 KEGG: Peptide

19.6 KEGG: Drug

19.7 KEGG: ATC

19.8 KEGG: Target-based Classification of Drugs

19.9 KEGG: JP15

19.10 KEGG: Animal Drugs

19.11 WHO ATC Classification System

19.12 ChemIDplus

19.13 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.14 ChEMBL Target Tree

19.15 UN GHS Classification

19.16 NORMAN Suspect List Exchange Classification

19.17 CCSBase Classification

19.18 EPA DSSTox Classification

19.19 LOTUS Tree

19.20 FDA Drug Type and Pharmacologic Classification

19.21 EPA Substance Registry Services Tree

19.22 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. Australian Industrial Chemicals Introduction Scheme (AICIS)
  2. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  3. DrugBank
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    https://www.drugbank.ca/legal/terms_of_use
  4. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  5. European Chemicals Agency (ECHA)
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    https://echa.europa.eu/web/guest/legal-notice
  6. Hazardous Substances Data Bank (HSDB)
  7. New Zealand Environmental Protection Authority (EPA)
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    https://www.epa.govt.nz/about-this-site/general-copyright-statement/
  8. CCSbase
    CCSbase Classification
    https://ccsbase.net/
  9. NORMAN Suspect List Exchange
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    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Oxytocin
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
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  11. LOTUS - the natural products occurrence database
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    https://lotus.nprod.net/
  12. NCI Thesaurus (NCIt)
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  13. Open Targets
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  14. ChEMBL
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    http://www.ebi.ac.uk/Information/termsofuse.html
  15. Comparative Toxicogenomics Database (CTD)
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    http://ctdbase.org/about/legal.jsp
  16. Drug Gene Interaction database (DGIdb)
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    http://www.dgidb.org/downloads
  17. IUPHAR/BPS Guide to PHARMACOLOGY
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    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  18. Therapeutic Target Database (TTD)
  19. ClinicalTrials.gov
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    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  20. DailyMed
  21. Drug Induced Liver Injury Rank (DILIrank) Dataset
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  22. European Medicines Agency (EMA)
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  23. Drugs and Lactation Database (LactMed)
  24. Drugs@FDA
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  25. WHO Model Lists of Essential Medicines
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  26. EU Clinical Trials Register
  27. FDA Approved Animal Drug Products (Green Book)
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  28. FDA Orange Book
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  29. Japan Chemical Substance Dictionary (Nikkaji)
  30. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
  31. Natural Product Activity and Species Source (NPASS)
  32. Metabolomics Workbench
  33. National Drug Code (NDC) Directory
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    https://www.fda.gov/about-fda/about-website/website-policies#linking
  34. Nature Chemical Biology
  35. NIPH Clinical Trials Search of Japan
  36. NLM RxNorm Terminology
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    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  37. PharmGKB
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    https://www.pharmgkb.org/page/policies
  38. Pharos
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  39. Springer Nature
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    https://creativecommons.org/licenses/by-nc-nd/4.0/
  41. WHO Anatomical Therapeutic Chemical (ATC) Classification
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  42. Wikidata
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  46. PubChem
  47. GHS Classification (UNECE)
  48. EPA Substance Registry Services
  49. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  50. PATENTSCOPE (WIPO)
  51. NCBI
CONTENTS