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Procainamide

PubChem CID
4913
Structure
Procainamide_small.png
Procainamide_3D_Structure.png
Molecular Formula
Synonyms
  • PROCAINAMIDE
  • 51-06-9
  • Novocainamide
  • Procaine amide
  • 4-amino-N-(2-diethylaminoethyl)benzamide
Molecular Weight
235.33 g/mol
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-18
Description
Procainamide is a benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias. It has a role as a sodium channel blocker, an anti-arrhythmia drug and a platelet aggregation inhibitor.
A derivative of procaine with less CNS action.
Procainamide is an Antiarrhythmic.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Procainamide.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

4-amino-N-[2-(diethylamino)ethyl]benzamide
Computed by Lexichem TK 2.7.0 (PubChem release 2024.11.20)

2.1.2 InChI

InChI=1S/C13H21N3O/c1-3-16(4-2)10-9-15-13(17)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3,(H,15,17)
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.3 InChIKey

REQCZEXYDRLIBE-UHFFFAOYSA-N
Computed by InChI 1.07.0 (PubChem release 2024.11.20)

2.1.4 SMILES

CCN(CC)CCNC(=O)C1=CC=C(C=C1)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C13H21N3O
Computed by PubChem 2.2 (PubChem release 2024.11.20)

2.3 Other Identifiers

2.3.1 CAS

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DrugBank ID

2.3.8 DSSTox Substance ID

2.3.9 HMDB ID

2.3.10 KEGG ID

2.3.11 Metabolomics Workbench ID

2.3.12 NCI Thesaurus Code

2.3.13 Nikkaji Number

2.3.14 NSC Number

2.3.15 PharmGKB ID

2.3.16 Pharos Ligand ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Amide, Procaine
  • Apo-Procainamide
  • Biocoryl
  • Hydrochloride, Procainamide
  • Novocainamide
  • Novocamid
  • Procainamide
  • Procainamide Hydrochloride
  • Procaine Amide
  • Procamide
  • Procan
  • Procan SR
  • Procanbid
  • Pronestyl
  • Rhythmin

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
235.33 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
XLogP3
Property Value
0.9
Reference
Computed by XLogP3 3.0 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Hydrogen Bond Acceptor Count
Property Value
3
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Rotatable Bond Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Exact Mass
Property Value
235.168462302 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Monoisotopic Mass
Property Value
235.168462302 Da
Reference
Computed by PubChem 2.2 (PubChem release 2024.11.20)
Property Name
Topological Polar Surface Area
Property Value
58.4 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Heavy Atom Count
Property Value
17
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
221
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2024.11.20)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
0
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)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Melting Point

165-169 °C
165 - 169 °C

3.2.3 Solubility

5050 mg/L
INSOL IN PETROLEUM ETHER /HYDROCHLORIDE SALT/
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 98
3.02e+00 g/L

3.2.4 LogP

0.88
HANSCH,C ET AL. (1995)
1.3

3.2.5 Dissociation Constants

Basic pKa
9.24
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
Basic pKa
9.35
Comparison of the accuracy of experimental and predicted pKa values of basic and acidic compounds. Pharm Res. 2014; 31(4):1082-95. DOI:10.1007/s11095-013-1232-z. PMID:24249037
pKa
9.32
SANGSTER (1994)

3.2.6 Collision Cross Section

154.85 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
Ross et al. JASMS 2022; 33; 1061-1072. DOI:10.1021/jasms.2c00111

3.2.7 Kovats Retention Index

Standard non-polar
2193 , 2193 , 2250 , 2199.8 , 2240 , 2245 , 2248
Semi-standard non-polar
2212.7 , 2226.2

3.2.8 Other Experimental Properties

FREELY SOL IN WATER; SOL IN ALCOHOL; SLIGHTLY SOL IN CHLOROFORM; VERY SPARINGLY SOL IN BENZENE, ETHER; MP: 165-169 °C; MAX ABSORPTION: 278 NM; PH OF 10% AQ SOLN: 5.5 /HYDROCHLORIDE SALT/
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 1005
WHITE TO TAN, CRYSTALLINE POWDER; ODORLESS /HYDROCHLORIDE SALT/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 794

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.3.1.1 Human Drugs
Breast Feeding; Milk, Human; Lactation; Antiarrhythmics
Human drug -> Discontinued
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 6
View All
NIST Number
125801
Library
Main library
Total Peaks
42
m/z Top Peak
86
m/z 2nd Highest
99
m/z 3rd Highest
120
Thumbnail
Thumbnail
2 of 6
View All
NIST Number
250658
Library
Replicate library
Total Peaks
18
m/z Top Peak
86
m/z 2nd Highest
99
m/z 3rd Highest
120
Thumbnail
Thumbnail

4.1.2 MS-MS

1 of 8
View All
Spectra ID
Ionization Mode
Positive
Top 5 Peaks

120.04501 100

92.04965 50.50

65.0386 14.90

163.08672 7.20

Thumbnail
Thumbnail
2 of 8
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

234.16178 100

92.05049 16.50

206.13076 3.30

161.07185 1.10

Thumbnail
Thumbnail

4.1.3 LC-MS

1 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M-H]-
Precursor m/z
234.1611863
Instrument
Thermo Q Exactive HF
Instrument Type
LC-ESI-QFT
Ionization Mode
negative
Collision Energy
HCD (NCE 20-30-40%)
Top 5 Peaks

234.16127 100

92.05061 20.40

206.13002 6.70

161.07216 3.30

135.0562 2.50

Thumbnail
Thumbnail
2 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
236.1757383
Instrument
Thermo Q Exactive HF
Instrument Type
LC-ESI-QFT
Ionization Mode
positive
Collision Energy
HCD (NCE 20-30-40%)
Top 5 Peaks

163.08655 100

236.17567 16.10

120.04442 11.50

100.11183 0.70

Thumbnail
Thumbnail

4.1.4 Other MS

Other MS
MASS: 1601 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)

4.2 UV Spectra

MAX ABSORPTION (PH 9.4 BORATE BUFFER): 272 NM (A= 578, 1%, 1 CM) /HCL SALT/
Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 836
MAX ABSORPTION (WATER): 278 NM /HYDROCHLORIDE SALT/
Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-183

4.3 Other Spectra

Intense mass spectral peaks: 86 m/z, 99 m/z, 120 m/z, 235 m/z
Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 384

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For the treatment of life-threatening ventricular arrhythmias.

7.2 LiverTox Summary

Procainamide is an oral antiarrhythmic agent that has been in use for more than 60 years. Long term procainamide therapy is known to induce hypersensitivity reactions, autoantibody formation and a lupus-like syndrome but is a rare cause of clinically apparent acute liver injury.

7.3 Drug Classes

Breast Feeding; Milk, Human; Lactation; Antiarrhythmics
Antiarrhythmic Agents

7.4 Clinical Trials

7.4.1 ClinicalTrials.gov

7.4.2 EU Clinical Trials Register

7.5 Therapeutic Uses

Anti-Arrhythmia Agents; Platelet Aggregation Inhibitors
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
PROCAINAMIDE IS USEFUL IN SUPPRESSING ARRHYTHMIAS OF VENTRICULAR ORIGIN, INCL VENTRICULAR EXTRASYSTOLES, PAROXYSMAL VENTRICULAR TACHYCARDIA, & VENTRICULAR FIBRILLATION. /HYDROCHLORIDE SALT/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 794
DRUG IS...EFFECTIVE AGAINST PAROXYSMAL ATRIAL TACHYCARDIA, ATRIAL FLUTTER, & ATRIAL TACHYCARDIA OR ATRIAL ECTOPIC SYSTOLES. IN CASES OF PAROXYSMAL ATRIAL TACHYCARDIA, OTHER MEASURES & AGENTS OF CHOICE SHOULD BE EMPLOYED BEFORE PROCAINAMIDE IS USED. /HYDROCHLORIDE SALT/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 794
PROCAINAMIDE HAS BEEN USED IN TREATMENT OF MYOTONIA, WHERE ITS EFFECTS RESEMBLE THOSE OF QUININE.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 696
For more Therapeutic Uses (Complete) data for PROCAINAMIDE (8 total), please visit the HSDB record page.

7.6 Drug Warnings

...USED WITH CAUTION & MEDICATION MUST BE STOPPED IF QRS COMPLEX IS EXCESSIVELY WIDENED. PROCAINAMIDE IS USUALLY WELL TOLERATED. HOWEVER, IT HAS OCCASIONALLY CAUSED SERIOUS SIDE EFFECTS, & DEATHS HAVE RESULTED.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
...PROCAINAMIDE CAN CAUSE UNTOWARD RESPONSES BY ITS ACTIONS ON ABNORMAL MYOCARDIUM OR AS RESULT OF CORRECTION OF ARRHYTHMIAS FOR WHICH DRUG IS ADMIN. ... PROCAINAMIDE...SHOULD NOT BE ADMIN WHEN COMPLETE A-V BLOCK IS PRESENT & SHOULD BE USED ONLY CAUTIOUSLY IN PRESENCE OF PARTIAL BLOCK BECAUSE OF DANGER OF ASYSTOLE.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
CROSS SENSITIVITY TO PROCAINE & RELATED DRUGS SHOULD BE ANTICIPATED. ... /IT/...MUST BE GIVEN CAUTIOUSLY IF PT IS DIGITALIZED. /HCL SALT/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 794
FATAL AGRANULOCYTOSIS...REPORTED, & FREQUENT BLOOD EXAM DURING CHRONIC... THERAPY ARE ESSENTIAL. SYNDROME SIMILAR TO SYSTEMIC LUPUS ERYTHEMATOSUS IS COMMON REACTION TO CHRONIC ADMIN, & MAY NECESSITATE TERMINATION OF THERAPY...
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 696
For more Drug Warnings (Complete) data for PROCAINAMIDE (9 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Procainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.

8.2 MeSH Pharmacological Classification

Voltage-Gated Sodium Channel Blockers
A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)
Anti-Arrhythmia Agents
Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)

8.3 FDA Pharmacological Classification

FDA UNII
L39WTC366D
Active Moiety
PROCAINAMIDE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Antiarrhythmic
FDA Pharmacology Summary
Procainamide is an Antiarrhythmic.

8.4 ATC Code

C - Cardiovascular system

C01 - Cardiac therapy

C01B - Antiarrhythmics, class i and iii

C01BA - Antiarrhythmics, class ia

C01BA02 - Procainamide

8.5 Absorption, Distribution and Excretion

Absorption
75 to 95%
Route of Elimination
Trace amounts may be excreted in the urine as free and conjugated p-aminobenzoic acid, 30 to 60 percent as unchanged PA, and 6 to 52 percent as the NAPA derivative.
Volume of Distribution
2 L/kg
PROCAINAMIDE IS RAPIDLY & ALMOST COMPLETELY ABSORBED FROM GI TRACT. WHEN... GIVEN ORALLY, ITS PLASMA CONCN BECOMES MAX IN ABOUT 60 MIN; AFTER IM ADMIN PEAK PLASMA CONCN ARE REACHED IN 15-60 MIN.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
AT ORDINARY PLASMA CONCN, ONLY 15%...IS BOUND TO MACROMOLECULAR CONSTITUENTS OF PLASMA. CONCN OF DRUG IN MOST TISSUES EXCEPT BRAIN IS GREATER THAN THAT IN PLASMA. APPROX 60% OF DRUG IS EXCRETED BY KIDNEY. TWO TO 10%...IS RECOVERED IN URINE AS FREE & CONJUGATED P-AMINOBENZOIC ACID.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
CONSIDERABLE DIFFERENCES...OBSERVED IN PROCAINAMIDE & ALSO PROCAINAMIDE ETHOBROMIDE DISPOSITION. ETHOBROMIDE IS CLEARED RAPIDLY IN BILE OF RATS & RABBITS, BUT ONLY SLOWLY IN DOGS. 64% OF ORALLY DOSED PROCAINAMIDE IS VOIDED AS UNCHANGED...IN HUMAN URINE, WHEREAS IN RHESUS MONKEY IT IS ALMOST COMPLETELY METABOLIZED.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 149
RENAL, CARDIAC, OR HEPATIC IMPARIMENT...RESULTED IN PROLONGED PLASMA HALF-LIVES, & THERE IS EVIDENCE THAT PROCAINAMIDE MAY INHIBIT ITS OWN ELIMINATION AFTER MULTIPLE DOSING.
The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 447
For more Absorption, Distribution and Excretion (Complete) data for PROCAINAMIDE (7 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Hepatic
DRUG IS RELATIVELY SLOWLY HYDROLYZED BY PLASMA ESTERASES.../PRC: AND BY MICROSOMAL ENZYMES/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
PROCAINAMIDE...WAS METABOLIZED TO N-ACETYL DERIV FOLLOWING ORAL ADMIN TO MAN & RHESUS MONKEYS. ... TWO MAJOR METABOLITES WERE DETECTED IN MONKEY URINE, P-ACETAMIDOBENZOIC ACID & DE-ETHYLATED DERIV, P-ACETAMIDO-N-[2-(ETHYLAMINO)-ETHYL]BENZAMIDE.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 553
N-ACETYLPROCAINAMIDE IS AN ACTIVE METABOLITE OF PROCAINAMIDE.
LEE ET AL; ANTI-ARRHYTHMIC EFFICACY OF N-ACETYLPROCAINAMIDE IN PATIENTS WITH PREMATURE VENTRICULAR CONTRACTIONS; CLIN PHARMACOL THER 19(MAY) 508-514 (1976)
Procainamide has known human metabolites that include Acecainide.
S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560

8.7 Biological Half-Life

~2.5-4.5 hours
PLASMA HALF-LIVES OF PARENT DRUG & ITS TWO MAJOR METABOLITES IN MAN IS BETWEEN 2 & 3 HR. ELIMINATION IS DIRECTLY RELATED TO CREATININE CLEARANCE, & PLASMA HALF-LIFE OF UNCHANGED DRUG IS CONSIDERABLY INCR IN CASES OF RENAL IMPAIRMENT.
The Chemical Society. Foreign Compound Metabolism in Mammals Volume 3. London: The Chemical Society, 1975., p. 149
...BIOLOGICAL HALF-LIFE IS 3-4 HR...
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695

8.8 Mechanism of Action

Procainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.
IV ADMIN...CAUSES FALL IN BLOOD PRESSURE; PERIPHERAL VASODILATATION PROBABLY CONTRIBUTES TO HYPOTENSIVE RESPONSE, BUT SYSTOLIC PRESSURE MAY BE REDUCED MORE THAN DIASTOLIC. ... CNS ACTIONS OF PROCAINAMIDE ARE NOT PROMINENT.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695

8.9 Human Metabolite Information

8.9.1 Cellular Locations

  • Cytoplasm
  • Membrane

8.9.2 Metabolite Pathways

8.10 Transformations

9 Use and Manufacturing

9.1 Uses

MEDICATION (VET)
MEDICATION

9.1.1 Use Classification

Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Methods of Manufacturing

...BY CONDENSING P-NITROBENZOYL CHLORIDE WITH BETA-DIETHYLAMINOETHYLAMINE & THEN REDUCING NITRO GROUP TO AMINO BY ANY OF USUAL METHODS. HYDROCHLORIDE FORMS READILY WHEN STREAM OF HYDROGEN CHLORIDE IS PASSED INTO SOLN OF BASE IN APPROPRIATE ORGANIC SOLVENT. /HYDROCHLORIDE SALT/
Osol, A. and J.E. Hoover, et al. (eds.). Remington's Pharmaceutical Sciences. 15th ed. Easton, Pennsylvania: Mack Publishing Co., 1975., p. 794

9.3 Formulations / Preparations

FOR ORAL ADMIN DRUG IS AVAILABLE AS PROCAINAMIDE HYDROCHLORIDE CAPSULES, USP, WHICH CONTAIN 250, 375, OR 500 MG OF DRUG. PROCAINAMIDE HYDROCHLORIDE INJECTION, USP, SUPPLIED IN 10-ML VIALS CONTAINING 100 MG/ML, IS SUITABLE FOR IM & IV INJECTION.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 694

9.4 General Manufacturing Information

COMMERCIALLY AVAILABLE AQ SOLN ARE PRESERVED WITH 0.9% BENZYL ALC & 0.09% SODIUM BISULFITE. /HYDROCHLORIDE SALT/
The Merck Index. 9th ed. Rahway, New Jersey: Merck & Co., Inc., 1976., p. 1005

10 Identification

10.1 Analytic Laboratory Methods

DRUG IS EXTRACTED FROM ALKALINIZED SAMPLE.../& ANALYZED BY GAS CHROMATOGRAPHY/... ACID SOLN /EXTRACTED/...EXAM SPECTROPHOTOMETRICALLY... CLARKE, EGC, ISOLATION & IDENTIFICATION OF DRUGS IN PHARMACEUTICALS: BODY FLUIDS AND POSTMORTEM MATERIALS, PHARMACEUTICAL PRESS, 1969, 512. /HCL SALT/
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 316
SPECTROPHOTOMETRIC METHOD... /HYDROCHLORIDE SALT/
Association of Official Analytical Chemists. Official Methods of Analysis. 10th ed. and supplements. Washington, DC: Association of Official Analytical Chemists, 1965. New editions through 13th ed. plus supplements, 1982., p. 13/664 38.224
RAPID FLUOROMETRIC DETERMINATION OF PROCAINAMIDE HYDROCHLORIDE DOSAGE FORMS.
TAN HSI, BEISER C; RAPID FLUOROMETRIC DETERMINATION OF PROCAINAMIDE HYDROCHLORIDE DOSAGE FORMS; J PHARM SCI 64(JUL) (1975)

10.2 Clinical Laboratory Methods

DRUG IS EXTRACTED FROM ALKALINIZED SAMPLE.../& ANALYZED BY GAS CHROMATOGRAPHY/... ACID SOLN /EXTRACTED/...EXAM SPECTROPHOTOMETRICALLY... CLARKE, EGC, ISOLATION & IDENTIFICATION OF DRUGS IN PHARMACEUTICALS: BODY FLUIDS AND POSTMORTEM MATERIALS, PHARMACEUTICAL PRESS, 1969, 512. /HCL SALT/
Sunshine, Irving (ed.) Methodology for Analytical Toxicology. Cleveland: CRC Press, Inc., 1975., p. 316
DETERMINATION OF PROCAINAMIDE IN BIOLOGICAL FLUIDS.
SIMONS KJ, LEVY RH; GLC DETERMINATION OF PROCAINAMIDE IN BIOLOGICAL FLUIDS; J PHARM SCI 64(DEC) 1967-1970 (1975)
GAS CHROMATOGRAPHIC METHOD FOR DETERMINATION OF PROCAINAMIDE IN BIOLOGICAL FLUIDS.
SIMONS ET AL; PHARMACOKINETICS OF PROCAINAMIDE IN NORMAL SUBJECTS USING A SPECIFIC GAS CHROMATOGRAPHIC ASSAY; RES COMMUN CHEM PATHO PHARMACOL 11: 173-175 (1975)
GAS LIQUID CHROMATOGRAPHY METHOD FOR DETERMINATION IN HUMAN SERUM.
LUDDEN ET AL; MICRODETERMINATION OF PROCAINAMIDE IN HUMAN SERUM; J PHARM SCI 67(MAR) 371-373 (1978)
For more Clinical Laboratory Methods (Complete) data for PROCAINAMIDE (7 total), please visit the HSDB record page.

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

Pictogram(s)
Irritant
Signal
Warning
GHS Hazard Statements

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]

H319 (100%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (100%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

Precautionary Statement Codes

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501

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

ECHA C&L Notifications Summary
The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Procainamide is an antiarrhythmic medication. Procainamide hydrochloride is a white to tan colored hygroscopic odorless crystalline powder. Soluble in water, alcohol, chloroform and practically insoluble in ether and benzene HUMAN EXPOSURE: Main risks and target organs: The heart is the main target organ. Procainamide is an antiarrhythmic agent used to suppress ventricular tachydysrhythmias. It increases the effective refractory period of the atria, and (to a lesser extent) that of the bundle of the His-Purkinje system and the ventricles. Toxic effects result from delay in conduction and depression of myocardial contractility, leading to cardiac dysrhythmia and cardiogenic shock. Its oral use is limited immunological adverse effects such as systemic lupus erythematosus in patients on chronic oral therapy. Summary of clinical effects: Cardiovascular System: Sinus or atrial tachycardias, atrioventricular and intraventricular block hypotension, cardiogenic shock, torsades de pointes and ventricular fibrillation. Central Nervous System: Lethargy, coma, respiratory arrest may result Gastrointestinal Tract: Nausea, vomiting, diarrhea and abdominal pain have been reported. Others: Anticholinergic effects, hypokalemia, metabolic acidosis and pulmonary edema. Indications: Suppression of ventricular arrhythmias. Treatment of automatic and reentrant supraventricular tachycardia. Supraventricular arrhythmias: Like quinidine, procainamide is only moderately effective in converting atrial flutter or chronic atrial fibrillation to sinus rhythm. The drug can be used to prevent recurrences of atrial flutter or atrial fibrillation after cardioversion. Procainamide is indicated in the treatment of ventricular premature contractions, and in preventing recurrence of ventricular tachycardia after conversion to sinus rhythm by intravenous drugs or by electrical cardioversion or by other antiarrhythmic therapy; also in preventing recurrence of paroxysmal supraventricular tachycardia, atrial fibrillation or flutter following conversion to sinus rhythm by initial vagotonic maneuvers, digitalis preparations, other pharmaceutical antiarrhythmic agents, or electrical cardioversion. The drug is useful in patients with severe ventricular arrhythmias who do not respond to lidocaine. Procainamide is useful for acute terminations of arrhythmias associated with the Wolff-Parkinson-White Syndrome. Procainamide is used in the treatment of cardiac arrhythmias occurring in patients during general anesthesia. The drug has been used in conjunction with hexamethonium bromide to produce controlled hypotension and, consequently, ischemia of sufficient degree for relatively bloodless field surgery. The injection of procainamide into painful soft tissues in fibrosis and radiculitis and into the periarticular tissues in degenerative arthritis provided relief for considerable periods. Contraindications: Complete heart block: because of its effects in suppressing nodal or ventricular pacemakers. Torsades de Pointes: administration of procainamide in such case may aggravate this special type of ventricular extrasystole or tachycardia instead of suppressing it. Idiosyncratic hypersensitivity: in patients sensitive to procaine or other ester-type local anesthetics, cross sensitivity to procainamide is unlikely. However, a previous allergic reaction to procainamide is a contraindication. Lupus erythematosus: aggravation of symptoms is highly likely. Precautions: Preferably, procainamide should not be used in patients with bronchial asthma or myasthenia gravis. Accumulation of the drug may occur in patients with heart, renal or liver failure. Procainamide may enhance the effects of antihypertensive agents, propranolol, and some skeletal muscle relaxants. Grave hypotension may follow intravenous administration of procainamide; it should be injected slowly under monitoring of blood pressure and ECG. Although procainamide has been used effectively in the treatment of ventricular dysrhythmias caused by digitalis intoxication, its effects are unpredictable and fatalities have occurred. Procainamide should not be administered to nursing mothers. Routes of entry: Oral: Oral route is a common route of entry in cases of poisoning. Parenteral: Toxicity reactions can occur after intravenous injections. Absorption by route of exposure: Oral: Procainamide is almost completely and rapidly absorbed from the gastrointestinal tract. Peak levels are reached within 1 hr after ingestion of capsules, but somewhat later after administration of tablets. The bioavailability is approximately 85%. An overdose may significantly delay intestinal procainamide absorption and prolong poisoning symptoms. With the sustained-release formulations, bioavailability is decreased and the absorption is delayed. The duration of action exceeds 8 hours. Intramuscular: Plasma concentrations showed very large variations. Procainamide appears in the plasma within two minutes and peak concentrations are reached within 25 minutes. Intravenous: Procainamide acts almost immediately, the plasma level declines 10 to 15% hourly. Distribution by route of exposure: About 20% of the procainamide in plasma is bound to proteins. Procainamide is rapidly distributed into most body tissues except the brain. In patients with cardiac failure or shock the volume of distribution may decrease. Procainamide crosses the placental barrier and has been reported to accumulate in the fetus. Biological half-life by route of exposure: Peak plasma levels: Oral: one to 2 hours after ingestion. Intramuscular: eighty minutes after administration. Intravenous: Within several minutes. The plasma half life after therapeutic doses is 3 to 4 hours. However, in one patient the overdose plasma half life was 8.8 hours. Congestive heart failure increases the plasma procainamide half life to 5 to 8 hours. The half-life is reduced in children and is prolonged in patients with renal insufficiency. Its major active metabolite, N-acetylprocainamide (NAPA), has a longer half-life than procainamide, from 6 hours up to 36 hours in overdoses. Metabolism: The major metabolic pathway of procainamide is hepatic N-acetylation. The rate of acetylation is determined genetically and shows a bimodal distribution into slow and fast acetylators. The major active metabolite, NAPA, has antiarrhythmic properties. Other urinary metabolites include desethyl-NAPA and desethyl-procainamide, which account for 8 to 15% of a dose of procainamide. The exact relationship between antiarrhythmic activity and plasma levels of NAPA has not been established. Up to 15% of the intravenous procainamide therapeutic dose is metabolized to NAPA, and 81% of the NAPA dose is excreted unchanged in urine. In fast acetylators or in renal insufficiency, 40% or more of a dose of procainamide may be excreted as NAPA, and its concentrations in plasma may equal or exceed those of the parent drug. Procainamide hydrochloride is only slightly hydrolyzed by plasma enzymes (to p-amino benzoic acid and diethylaminoethylamine). Elimination by route of exposure: Procainamide is excreted in the urine with about 50% as unchanged procainamide, and up to about 30% as NAPA (less in slow acetylators). Since the elimination of both the parent drug and metabolites is almost entirely by renal excretion, they can accumulate to dangerous levels when renal failure or congestive heart failure is present. After an overdose, hepatic biotransformation probably is a more important elimination pathway than renal excretion. Following an overdose, the elimination half-life (in the presence of a serum creatinine of 5.8 mg/dL) of NAPA increased from 6 to 35.9 hours while the procainamide elimination increased from 3 to 10.5 hours. Mode of action: Toxicodynamics: Toxic effects result from quinidine-like effect with delay of conduction and depression of myocardial contractility. Contractility of the undamaged heart is usually not affected by therapeutic concentrations, although slight reduction of cardiac output may occur, and may be significant in the presence of myocardial damage. High toxic concentrations may prolong atrioventricular conduction time or induce atrioventricular block or even cause abnormal automaticity and spontaneous firing, by unknown mechanisms. The toxic mechanism of the drug is dose dependent and is related to depression of contractility, decreased vascular resistance secondary to direct vasodilatation and some alpha adrenergic blocking. Besides the cardiovascular effects, procainamide produces CNS depression and has anticholinergic effects. Pharmacodynamics: Procainamide is an antiarrhythmic agent with electrophysiological properties similar to that of quinidine. Procainamide increases the effective refractory period of the atria, of the bundle of His-Purkinje system and of the ventricles. It reduces impulse conduction velocity in atria, His-Purkinje fibers, and ventricular muscle. But it has also variable effects on the atrioventricular node, a direct slowing action and a weaker vagolytic effect which may speed atrio-conduction slightly. Myocardial excitability is reduced in the atria, Purkinje fibers, papillary muscles, and ventricles by an increase in the threshold for excitation. NAPA is less potent than procainamide, and some of its cardiac actions are qualitatively different. Procainamide does not produce alpha-adrenergic blockade, but, in the dog, it can block autonomic ganglia weakly and cause a measurable impairment of cardiovascular reflexes. Human data: Adults: A single oral dose may produce symptoms of toxicity. Ingestion of 3 gm may be dangerous, especially if patient is slow acetylator or has renal impairment or underlying heart disease. Death was reported from intravenous administration. Interactions: If other antiarrhythmic drugs are being used, additive effects on the heart may occur with procainamide administration, and dosage reduction may be necessary. Anticholinergic drugs administered concurrently with procainamide may produce additive antivagal effects on A-V nodal conduction. Patients taking procainamide who require neuromuscular blocking agents such as succinylcholine may require less than usual doses of the latter, due to procainamide effect on reducing acetylcholine release. The neuromuscular blocking activity of an antibiotic having such action may be accentuated by procainamide. The hypotensive action of antihypertensive agents, including thiazide diuretics, may be potentiated by procainamide. Cimetidine therapy given to older male patients taking procainamide may increase steady-state concentrations of procainamide. Main adverse effects: The side-effects most frequently reported after high dosage of procainamide include anorexia, diarrhea, nausea, and vomiting. Intravenous administration may cause hypotension, ventricular fibrillation or asystole if the injection is too rapid. Following chronic administration, systemic lupus erythematosus-like syndrome may develop. Other side effects which have been reported include mental depression, dizziness, psychosis with hallucinations, joint and muscle pain, muscular weakness, a bitter taste, flushing, skin rashes, pruritus, angioneurotic edema and hypersensitivity leading to chills, fever and urticaria. Leucopenia and agranulocytosis have followed repeated use of procainamide. Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. High concentrations of procainamide in plasma can produce ventricular premature depolarization, ventricular tachycardia, or ventricular fibrillation. Hepatomegaly with increased serum aminotransferase level has been reported after a single oral dose. Mild hypovolemia, hypokalemia, metabolic acidosis may occur. Increased QT interval and prolonged QRS together with hypotension are sensitive indexes of serious poisoning. Parenteral administration of procainamide should be monitored electrocardiographically to give evidence of impending heart block. Acute poisoning: Ingestion: Serious toxic effects include conduction disturbances (QRS, QT prolongations), ventricular arrhythmias and cardiogenic shock. Increased ventricular extrasystoles, ventricular tachycardia (especially of the "torsades de pointes" type) or fibrillation may occur. The threshold of cardiac pacing is increased and the heart may even be nonresponsive. Lethargy, confusion and coma may occur. Other toxic manifestations are pulmonary edema, respiratory depression, urticaria, pruritus, nausea, vomiting, diarrhea and abdominal pain. Psychosis with hallucinations have been reported occasionally. Parenteral exposure: Intravenous administration may cause hypotension, ventricular fibrillation or asystole if the injection is too rapid. Chronic poisoning: Ingestion: A lupus erythematosus like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions is fairly common after prolonged procainamide administration. Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. Agranulocytosis has occurred after repeated use of procainamide. Course, prognosis, cause of death: Presence of PVCs and runs of ventricular tachycardia that are almost always successfully treated. Prognosis is usually good if there is not progress to ventricular fibrillation or asystole. Death is due to ventricular fibrillation or asystole. Long-term effects are agranulocytosis from hypersensitivity reaction, which is associated with 90% recovery rate. Systematic description of clinical effects: Cardiovascular: Acute: Sinus or atrial tachycardia due to the vagolytic effects. Conduction disturbances such as atrioventricular block, intraventricular block. Ventricular arrhythmias, including torsades de pointes, ventricular tachycardia and fibrillation. Hypotension and cardiogenic shock. ECG may show widening QRS, atrioventricular block, prolongation of QT interval and ventricular arrhythmia. Chronic: Chronic exposure may also produce arrhythmias. Cardiac tamponade due to pericarditis has been reported in a case of procainamide induced systemic lupus syndrome. Respiratory: Acute: Respiratory arrest and pulmonary edema. Neurological: Central nervous system (CNS): Acute: Dizziness or giddiness, weakness, mental depression, and psychosis with hallucinations have been reported occasionally. Lethargy may progress to coma. Skeletal and smooth muscle: Chronic: Skeletal muscular weakness and diaphragmatic paralysis has been reported in a case. Gastrointestinal: Acute: Anorexia, nausea, vomiting, abdominal pain, bitter taste, or diarrhea may occur in 3 to 4% of patients taking oral procainamide. Chronic: Nausea, vomiting may be seen. Hepatic: Acute: Hepatomegaly with increased serum aminotransferase level has been reported after a single oral dose. Dermatological: Chronic: Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rashes. Eye, ear, nose, throat: local effects: Acute: Blurred vision has been reported. Hematological: Chronic: Neutropenia, thrombocytopenia, or hemolytic anemia and agranulocytosis may rarely be encountered. Immunological: Chronic: Systemic lupus erythematosus like syndrome has been reported. Metabolic: Acid-base disturbances: Acute: Metabolic acidosis has been reported. Fluid and electrolyte disturbances: Acute: Hypokalemia may occur. Angioneurotic edema and maculopapular rashes have been reported. Special risks: Pregnancy: It is not known whether procainamide cause fetal harm when administered to a pregnant woman. Procainamide should be given to a pregnant woman only if clearly needed. Breast feeding: Both procainamide and NAPA are excreted in human milk. Therefore, procainamide should be given to a nursing mother only if clearly needed. Pediatric use: Safety and effectiveness in children have not been established. Plasma levels of NAPA may rise disproportionately in patients with renal impairment, because it is more dependent than procainamide on renal excretion for elimination. Elimination: Renal elimination of procainamide appears not to be affected by urinary pH or by urinary flow rate. However, because procainamide and NAPA are substantially eliminated by the kidney, it is important to maintain adequate renal functions.
International Programme on Chemical Safety; Poisons Information Monograph: Procainamide (PIM 436) (1992) Available from, as of December 6, 2005: https://www.inchem.org/pages/pims.html

12.1.2 Hepatotoxicity

In clinical trials, procainamide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, procainamide has only rarely been linked to cases of clinically apparent liver injury. In reported cases, fever and mild symptoms arose within 1 to 3 weeks of starting (or within 1 day of restarting) procainamide, associated with a cholestatic pattern of serum enzyme elevations with mild or no jaundice (Case 1). Immunoallergic features were usually present (fever, rash, leukocytosis). In reported cases, fever resolved immediately and evidence of liver injury within a few days to weeks of stopping procainamide. Liver biopsy may how granulomas in addition to mild nonspecific changes. Interestingly, the hepatotoxicity of procainamide closely resembles that of quinidine, but there is no apparent cross sensitivity to the hepatic injury. In addition, up to 20% of patients on long term procainamide therapy develop autoantibodies, including ANA and LE prep positivity and a proportion develop a “lupus-like” syndrome. These autoimmune conditions, however, typically occur without an accompanying hepatitis, serum enzyme elevations or jaundice.

Likelihood score: C (probable rare cause of clinically apparent liver injury).

12.1.3 Drug Induced Liver Injury

Compound
procainamide
DILI Annotation
Less-DILI-Concern
Severity Grade
4
Label Section
Adverse reactions
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

12.1.4 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Maternal doses of procainamide 2 grams daily produced low levels of the drug and its active metabolite in the milk of one mother. Although it would not be expected to cause adverse effects in older breastfed infants, the relative lack of data concerning breastfeeding during maternal procainamide therapy would argue for careful monitoring if this drug is used while breastfeeding a neonate possibly Measurement of infant serum levels could help to rule out toxicity if there is a concern.

◉ Effects in Breastfed Infants

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

◉ Effects on Lactation and Breastmilk

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

12.1.5 Acute Effects

12.1.6 Interactions

STUDIES HAVE DEMONSTRATED THAT PROCAINAMIDE IN CATS...MAY PROLONG & INTENSIFY NEUROMUSCULAR BLOCKADE PRODUCED BY SUCCINYLCHOLINE.
Evaluations of Drug Interactions. 2nd ed. and supplements. Washington, DC: American Pharmaceutical Assn., 1976, 1978., p. 600

12.1.7 Human Toxicity Excerpts

...IT HAS OCCASIONALLY CAUSED SERIOUS SIDE EFFECTS, & DEATHS HAVE RESULTED. WHEN...GIVEN ORALLY, MOST FREQUENTLY OBSERVED...EFFECTS ARE ANOREXIA, NAUSEA, & VOMITING. FLUSHING, BITTER TASTE, DIARRHEA, WEAKNESS, MENTAL DEPRESSION, GIDDINESS, & PSYCHOSIS WITH HALLUCINATIONS...ALSO...REPORTED.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
HYPERSENSITIVITY TO DRUG, CHILLS, FEVER, JOINT & MUSCLE PAIN, MALAISE, ITCHING, ANGIOEDEMA, & URTICARIAL OR MACULOPAPULAR SKIN RASH HAVE...OCCURRED. ... FATAL AGRANULOCYTOSIS...REPORTED... /ORAL ADMIN/
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695
...IV ADMIN... HYPOTENSION COMMONLY OCCURS & CAN RESULT IN CARDIOVASCULAR COLLAPSE, CONVULSIONS, & CORONARY INSUFFICIENCY. SERIOUS DISTURBANCES OF CARDIAC RHYTHM, SUCH AS VENTRICULAR ASYSTOLE OR FIBRILLATION... HYPOTENSION MAY OCCUR AFTER IM /ADMIN/, BUT IT IS USUALLY NOT SEVERE.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 696

12.1.8 Non-Human Toxicity Excerpts

...RAPID IV INJECTION OF LARGE DOSES IN ANIMALS CAUSES TREMORS & DEATH MAY RESULT FROM RESP DEPRESSION.
Goodman, L.S., and A. Gilman. (eds.) The Pharmacological Basis of Therapeutics. 5th ed. New York: Macmillan Publishing Co., Inc., 1975., p. 695

12.1.9 Protein Binding

15 to 20%

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 Chemical Co-Occurrences in Literature

14.6 Chemical-Gene Co-Occurrences in Literature

14.7 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 Chemical-Target Interactions

16.2 Drug-Drug Interactions

16.3 Drug-Food Interactions

  • Avoid alcohol.
  • Take with food. Food reduces irritation.

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Classification

18.1 MeSH Tree

18.2 NCI Thesaurus Tree

18.3 ChEBI Ontology

18.4 KEGG: ATC

18.5 KEGG: Target-based Classification of Drugs

18.6 KEGG: Drug Groups

18.7 WHO ATC Classification System

18.8 FDA Pharm Classes

18.9 ChemIDplus

18.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

18.11 ChEMBL Target Tree

18.12 UN GHS Classification

18.13 NORMAN Suspect List Exchange Classification

18.14 CCSBase Classification

18.15 EPA DSSTox Classification

18.16 MolGenie Organic Chemistry Ontology

19 Information Sources

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  14. CCSbase
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  17. LiverTox
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  20. ClinicalTrials.gov
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  21. Therapeutic Target Database (TTD)
  22. Drug Induced Liver Injury Rank (DILIrank) Dataset
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    https://www.norman-network.com/nds/SLE/
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  27. NIST Mass Spectrometry Data Center
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    https://www.nist.gov/srd/public-law
  28. Japan Chemical Substance Dictionary (Nikkaji)
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    Anatomical Therapeutic Chemical (ATC) classification
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  45. MolGenie
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  46. PATENTSCOPE (WIPO)
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CONTENTS