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Pemoline

PubChem CID
4723
Structure
Pemoline_small.png
Pemoline_3D_Structure.png
Molecular Formula
Synonyms
  • pemoline
  • Phenoxazole
  • Phenylisohydantoin
  • Azoksodon
  • Fenoxazol
Molecular Weight
176.17 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-25
  • Modify:
    2025-01-11
Description
Pemoline is a member of the class of 1,3-oxazoles that is 1,3-oxazol-4(5H)-one which is substituted by an amino group at position 2 and by a phenyl group at position 5. A central nervous system stimulant, it was used to treat hyperactivity disorders in children, but withdrawn from use following reports of serious hepatotoxicity. It has a role as a central nervous system stimulant.
Pemoline is a DEA Schedule IV controlled substance. Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III. It is a Stimulants substance.
In 2005, the Food and Drug Administration (FDA) withdrew approval for pemoline. In March 2005, Abbott Laboratories (Cylert marketer) had discontinued the production of Cylert arguing economic reasons.

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Pemoline.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

2-amino-5-phenyl-1,3-oxazol-4-one
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C9H8N2O2/c10-9-11-8(12)7(13-9)6-4-2-1-3-5-6/h1-5,7H,(H2,10,11,12)
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NRNCYVBFPDDJNE-UHFFFAOYSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1=CC=C(C=C1)C2C(=O)N=C(O2)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C9H8N2O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 Deprecated CAS

101053-01-4, 2933-45-1

2.3.3 European Community (EC) Number

2.3.4 UNII

2.3.5 ChEBI ID

2.3.6 ChEMBL ID

2.3.7 DEA Code Number

1530 (DEA schedule IV controlled substance)

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 KEGG ID

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 PharmGKB ID

2.3.17 Pharos Ligand ID

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Compounds, Pemoline
  • Cylert
  • Magnesium, Pemoline
  • PemADD
  • Pemoline
  • Pemoline Compounds
  • Pemoline Magnesium
  • Phenoxazole
  • Phenylisohydantoin
  • Tradon

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
176.17 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
0.9
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
1
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
176.058577502 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
176.058577502 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
64.7 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
13
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
244
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
0
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
1
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 Color / Form

Crystals
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1221
White crystalline powder
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 367

3.2.2 Taste

Tasteless
Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 367

3.2.3 Melting Point

256 dec °C
PhysProp
Decomp: 256-257 °C
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1221

3.2.4 Solubility

Practically insol in ether, acetone, dil hydrochloric acid; sol in propylene glycol (1%) and hot alcohol
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1221

3.2.5 LogP

0.7

3.2.6 Decomposition

When heated to decomposition it emits toxic fumes of /Nitrogen oxide/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2075

3.2.7 Dissociation Constants

pKa = 10.5
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1308

3.2.8 Kovats Retention Index

Standard non-polar
2055 , 2080

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Synthetic Cannabinoids or Psychoactive Compounds
S58 | PSYCHOCANNAB | Synthetic Cannabinoids and Psychoactive Compounds | DOI:10.5281/zenodo.3247723
3.3.1.1 Human Drugs
Human drug -> Discontinued
Human drug -> Discontinued; Active ingredient (PEMOLINE)
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

4 Spectral Information

4.1 1D NMR Spectra

1D NMR Spectra

4.1.1 1H NMR Spectra

Instrument Name
Varian CFT-20
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
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4.2 Mass Spectrometry

4.2.1 GC-MS

1 of 7
View All
NIST Number
247954
Library
Main library
Total Peaks
68
m/z Top Peak
107
m/z 2nd Highest
176
m/z 3rd Highest
89
Thumbnail
Thumbnail
2 of 7
View All
NIST Number
42429
Library
Replicate library
Total Peaks
86
m/z Top Peak
107
m/z 2nd Highest
90
m/z 3rd Highest
176
Thumbnail
Thumbnail

4.2.2 MS-MS

1 of 5
View All
Spectra ID
Ionization Mode
Negative
Top 5 Peaks

41.0155 100

175.04285 1.15

41.01101 1.09

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

106.06784 100

79.05686 41.64

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4.3 UV Spectra

UV: 989 (Absorption Spectra in the UV and visible Regions, Academic Press, New York)
Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V1 949

4.4 IR Spectra

4.4.1 FTIR Spectra

1 of 2
Instrument Name
Bio-Rad FTS
Technique
KBr0
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
01339
Lot Number
16901
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail
2 of 2
Technique
BETWEEN SALTS
Source of Sample
The Baker Castor Oil Company
Copyright
Copyright © 1980, 1981-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

4.4.2 ATR-IR Spectra

Instrument Name
Bio-Rad FTS
Technique
ATR-Neat (DuraSamplIR II)
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
01339
Lot Number
16901
Copyright
Copyright © 2009-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

4.5 Raman Spectra

Technique
FT-Raman
Source of Spectrum
Forensic Spectral Research
Source of Sample
Alltech Associates, Inc., Grace Davison Discovery Sciences
Catalog Number
01339
Lot Number
16901
Copyright
Copyright © 2012-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
Thumbnail

4.6 Other Spectra

Intense mass spectral peaks: 90 m/z, 118 m/z, 190 m/z, 204 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. 310

6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

For treatment of Attention Deficit Hyperactivity Disorder (ADHD)

7.2 FDA Approved Drugs

7.3 FDA Orange Book

7.4 Clinical Trials

7.4.1 ClinicalTrials.gov

7.5 DEA Drug and Chemical Information

7.5.1 DEA Controlled Substances

Substance
Pemoline
DEA Controlled Substances Code Number
1530
Controlled Substances Act Schedule
Schedule IV - Substances in the DEA Schedule IV have a low potential for abuse relative to substances in Schedule III.
Class
Stimulants

7.6 Therapeutic Uses

Central Nervous System Stimulants
National Library of Medicine's Medical Subject Headings online file (MeSH, 1999)
The Agency has concluded that the overall risk of liver toxicity from Cylert and generic pemoline products outweighs the benefits of this drug. In May 2005, Abbott chose to stop sales and marketing of Cylert in the U.S. All generic companies have also agreed to stop sales and marketing of this product (Pemoline tablets and chewable tablets). Cylert is a central nervous system stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). This product is considered second line therapy for ADHD because of its association with life threatening hepatic failure.
FDA; Center for Drug Evaluation and Research; Alert for Healthcare Professionals, Pemoline Tablets and Chewable Tablets (marketed as Cylert) (October 2005). Available from, as of January 15, 2008: https://www.fda.gov/cder/drug/InfoSheets/HCP/pemolineHCP.htm
Adjunct to psychological, educational, social, and other remedial measures in the treatment of attention deficit disorder with hyperactivity (hyperkinetic syndrome of childhood, minimal brain dysfunction) in carefully selected children older than 6 years of age. /Use is included in the labeling approved by the US Food and Drug Administration/.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
Pemoline has been used in the treatment of fatigue, mental depressions, and chronic schizophrenia, and as a mild stimulant for geriatric patients. /Uses are not included in the labeling approved by the US Food and Drug Administration/.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309

7.7 Drug Warnings

The Agency has concluded that the overall risk of liver toxicity from Cylert and generic pemoline products outweighs the benefits of this drug. In May 2005, Abbott chose to stop sales and marketing of Cylert in the U.S. All generic companies have also agreed to stop sales and marketing of this product (Pemoline tablets and chewable tablets). Cylert is a central nervous system stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). This product is considered second line therapy for ADHD because of its association with life threatening hepatic failure.
FDA; Center for Drug Evaluation and Research; Alert for Healthcare Professionals, Pemoline Tablets and Chewable Tablets (marketed as Cylert) (October 2005). Available from, as of January 15, 2008: https://www.fda.gov/cder/drug/InfoSheets/HCP/pemolineHCP.htm
Because of its association with life threatening hepatic failure, Cylert should not ordinarily be considered as first line drug therapy for ADHD. Because Cylert provides an observable symptomatic benefit, patients who fail to show substantial clinical benefit within 3 weeks of completing dose titration, should be withdrawn from Cylert therapy.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
Treatment with Cylert should be initiated only in individuals without liver disease and with normal baseline liver function tests. It is not clear if baseline and periodic liver function testing are predictive of these instances of acute liver failure; however, it is generally believed that early detection of drug induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery. Accordingly, the following liver monitoring program is recommended: Serum ALT (SGPT) levels should be determined at baseline, and every two weeks thereafter. If Cylert therapy is discontinued and then restarted, liver function test monitoring should be done at baseline and reinitiated at the frequency above. Cylert should be discontinued if serum ALT (SGPT) is increased to a clinically significant level, or any increase > or = 2 times the upper limit of normal, or if clinical signs and symptoms suggest liver failure
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
Clinical experience suggests that in psychotic children, administration of Cylert may exacerbate symptoms of behavior disturbance and thought disorder.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
For more Drug Warnings (Complete) data for PEMOLINE (16 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Pemoline belongs to the group of medicines called central nervous system (CNS) stimulants. It is used to treat attention deficit hyperactivity disorder (ADHD). Pemoline stimulates the brain, probably by affecting neurotransmitters, the chemicals in the brain that nerves use to communicate with each other.

8.2 MeSH Pharmacological Classification

Central Nervous System Stimulants
A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. (See all compounds classified as Central Nervous System Stimulants.)

8.3 ATC Code

N - Nervous system

N06 - Psychoanaleptics

N06B - Psychostimulants, agents used for adhd and nootropics

N06BA - Centrally acting sympathomimetics

N06BA05 - Pemoline

8.4 Absorption, Distribution and Excretion

Absorption
Pemoline is rapidly absorbed from the gastrointestinal tract
Route of Elimination
Pemoline is excreted primarily by the kidneys with approximately 50% excreted unchanged and only minor fractions present as metabolites.
Pemoline is rapidly absorbed from the gastrointestinal tract. Approximately 50% is bound to plasma proteins. The serum half-life of pemoline is approximately 12 hours. Peak serum levels of the drug occur within 2 to 4 hours after ingestion of a single dose. Multiple dose studies in adults at several dose levels indicate that steady state is reached in approximately 2 to 3 days. In animals given radiolabeled pemoline, the drug was widely and uniformly distributed throughout the tissues, including the brain.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
... Pemoline and its metabolites are excreted primarily in urine; only negligible amounts are excreted in feces. About 75% of an oral dose is excreted in urine within 24 hr; about 43% is excreted unchanged and about 22% is excreted as pemoline conjugates.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
Pemoline is absorbed from the GI tract, and peak serum concentrations are achieved within 2-4 hours. Multiple-dose studies in adults indicate that serum concentrations plateau in about 3 days. In a study involving adults, the CNS stimulant effect of a single oral dose of pemoline was relatively long, reaching its peak within 4 hr and lasting at least 8 hr. However, when pemoline is administered to children in the treatment of attention deficit disorder, the drug has a gradual onset of action and therapeutic effects may not be apparent until 2 or 3 weeks of therapy.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1308

8.5 Metabolism / Metabolites

Hepatic
Pemoline is metabolized by the liver. Metabolites of pemoline include pemoline conjugate, pemoline dione, mandelic acid, and unidentified polar compounds. Cylert is excreted primarily by the kidneys with approximately 50% excreted unchanged and only minor fractions present as metabolites.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf

8.6 Biological Half-Life

The serum half-life of pemoline is approximately 12 hours.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
Following a single oral dose in healthy adults, the plasma or serum half-life of pemoline has ranged from about 9-14 hr. Following a single oral dose in children, the plasma elimination half-life exhibits considerable interindividual variation, ranging from about 2-12 hr (mean: 8.6 hr). Preliminary evidence suggests that the drug may exhibit nonlinar kinetics in children following multiple dosing, with the elimination half-life increasing substantially. ...
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309

8.7 Mechanism of Action

The pharmacologic actions of pemoline are qualitatively similar to those of the amphetamines and methylphenidate, and include CNS and respiratory stimulation and weak sympathomimetic activity. ... Limited animal experiments suggest that the CNS stimulatory action of pemoline may be mediated by brain dopamine. Pemoline may produce an increase in motor activity, mental alertness, diminished sense of fatigue, and mild euphoria. ... In usual therapeutic dosage, pemoline exhibits no substantial effects on the peripheral circulatory system.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
Cylert (pemoline) has a pharmacological activity similar to that of other known central nervous system stimulants; however, it has minimal sympathomimetic effects. Although studies indicate that pemoline may act in animals through dopaminergic mechanisms, the exact mechanism and site of action of the drug in man is not known.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf

9 Use and Manufacturing

9.1 Uses

This is a /DEA:/ Schedule IV controlled substance.
21 CFR 1308.14(e) (USDEA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 20, 2008: https://www.ecfr.gov
Therapeutic Category: CNS Stimulant /Former/
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 1221
MEDICATION /Former/

9.1.1 Use Classification

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Pharmaceuticals
S72 | NTUPHTW | Pharmaceutically Active Substances from National Taiwan University | DOI:10.5281/zenodo.3955664

9.2 Formulations / Preparations

Cylert, oral, chewable tablets with pemoline 37.5 mg and povidone.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1310

9.3 General Manufacturing Information

Discontinued for use in the United States in October 2005
FDA Alert 10/05. Alert for Healthcare Professionals Pemoline Tablets and Chewable Tablets (marketed as Cylert) Available from, as of Jan 8, 2008: https://www.fda.gov/CDER/drug/InfoSheets/HCP/pemolineHCP.htm

10 Identification

10.1 Analytic Laboratory Methods

A rapid method for the detn of banned drugs in sport (including stimulants, anabolic steroids, and diuretics) based on micellar liquid chromatography is proposed. The mobile phase is an aq soln of a surfactant (sodium dodecyl sulfate in this instance) and the stationary phase is octadecylsilica. The retention parameters of the drugs were established and the effect of a mobile phase organic modifier on the chromatography behavior of the cmpd was studied. Improvements in efficiency were achieved by control of the temp of the mobile phase. This method allows the direct injection of urine samples for the detn of drugs excreted free in urine: amiphenazole, amiloride, amphetamine, clostebol, ephedrine, phenylpropanolamine, metandienone, methoxyphenamine, nandrolone, and spironolactone. Limits of detection in the nanogram range and relative standard deviations of 1-11% were obtained.
Carretero I et al; Anal Chim Acta 259 (2): 203-10 (1992)
Pemoline and cyproheptadine in cmpd tablets dissolved in diluted hydochloric acid soln were detected by UV spectrophotometry at 262 and 286 nm, respectively; the average recovery was 102.1 and 100.8%, respectively.
Zhou X; Zhongguo Yaoke Daxue Xuebao 20 (5): 1989,307-8
Pemoline was determined in tablets by HPLC on a reversed-phase column (10 um C18) with H2O-MeOH (77:23) as the mobile phase and UV detection at 216 nm. Caffeine was used as the internal standard. Linearity was shown over the concn. range 5-35 mg/l. The relative standard deviation and recovery were 1.9 and 99.8-104.8%, respectively.
Bobarevic N et al; Acta Pharm Jugosl 38 (1): 31-4 (1988)
Analyte: pemoline; matrix: pharmaceutical preparation; procedure: capillary electrophoresis with ultraviolet detection at 214 nm
Dong Y et al; Chromatographia 48: 310-313 (1998). As cited in: Lunn G; HPLC and CE Methods for Pharmaceutical Analysis. CD-ROM. New York, NY: John Wiley & Sons (2000)

10.2 Clinical Laboratory Methods

GAS LIQUID CHROMATOGRAPHY METHOD FOR PEMOLINE WAS STUDIED IN SPIKED HUMAN URINE & PLASMA & IN BLOOD & URINE FROM VOLUNTEER FOLLOWING 40 MG DOSE.
LIBEER JC, SCHEPENS P; J PHARM SCI 67 (MAR): 419-21 (1979)
SENSITIVE GAS LIQUID CHROMATOGRAPHY ASSAY FOR PEMOLINE IN BIOLOGICAL FLUIDS USING NITROGEN SPECIFIC DETECTION.
HOFFMAN DJ; J PHARM SCI 68 (4): 445-7 (1979)
ASSAY OF PEMOLINE IN HUMAN PLASMA, SALIVA & URINE BY CAPILLARY GAS CHROMATOGRAPHY WITH NITROGEN SELECTIVE DETECTION.
VERMEULEN NP E ET AL; J CHROMATOGR 157 (1): 133-40 (1978)
The surface-enhanced Raman spectra of stimulant drugs, including mefenorex, pentylenetetrazole, L-amphetamine and pemoline, were obtained on colloidal silver. Silver colloids are prepared in a single step, at room temp, by chemical reduction of Ag+ with sodium tetrahydroborate. Spectra are recorded using drug concn at the ug/ml level. Individual drugs can be identified by characteristic vibrational bands. The surface-enhanced Raman spectrum o human urine and that of human urine spiked with mixt of stimulant drugs are reported.
Ruperez A et al; Vib Spectrosc 2 (2-3): 145-54 (1991)
For more Clinical Laboratory Methods (Complete) data for PEMOLINE (6 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]

H312 (100%): Harmful in contact with skin [Warning Acute toxicity, dermal]

H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]

Precautionary Statement Codes

P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, 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 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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 (100%)

Acute Tox. 4 (100%)

Acute Tox. 4 (100%)

11.2 Accidental Release Measures

11.2.1 Disposal Methods

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

11.3 Handling and Storage

11.3.1 Storage Conditions

Tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably at 15 to 30 °C. ... Expiration date /is/ 5 years following the date of manufacture.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1308

11.4 Regulatory Information

DEA Controlled Substances
DEA schedule IV controlled substance
New Zealand EPA Inventory of Chemical Status
4(5H)-Oxazolone, 2-amino-5-phenyl-: Does not have an individual approval but may be used under an appropriate group standard

11.4.1 FDA Requirements

Schedule IV shall consist of the drugs and other substances, by whatever official name, common or usual name, chemical name, or brand name designated, listed in this section. Each drug or substance has been assigned the DEA Controlled Substances Code Number set forth opposite it. Stimulants: Unless specifically excepted or unless listed in another schedule, any material, compound, mixture, or preparation which contains any quantity of the following substances having a stimulant effect on the central nervous system, including its salts, isomers and salts of isomers: Pemoline (including organometallic complexes and chelates thereof) (DEA Code Number: 1530) is included on this list.
21 CFR 1308.14(e) (USFDA); U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from, as of March 13, 2008: https://www.ecfr.gov
The Approved Drug Products with Therapeutic Equivalence Evaluations List currently identifies pemoline as a discontinued drug product.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 15, 2005: https://www.fda.gov/cder/ob/

11.5 Other Safety Information

11.5.1 Special Reports

International Programme on Chemical Safety; Poisons Information Monograph: Pemoline (PIM 940) (1998) Available from http://www.inchem.org/pages/pims.html as of January 23, 2008
Langer DH et al; Evidence of Lack of Abuse or Dependence Following Pemoline Treatment: Results of a Retrospective Survey. Drug Alcohol Depend 17 (2-3): 213-27 (1986). Pemoline is recognized as an efficacious and safe therapeutic agent for children suffering from attention deficit disorder. A review of adverse experience reports suggests that pemoline has a limited potential for abuse or dependence. ... Human experience indicates that, despite the fact that the drug has been available in the U.S. since 1975, use is limited and is increasing slowly. A review of the literature revealed no published case reports of euphoria, abuse, dependence or withdrawal. While there have been a few reports of tolerance, it is possible that these were a reflection of inadequate dosing rather than actual tolerance to the drug's therapeutic effects. During the 10 yr that pemoline has been available in the United States, there have been only four reports of withdrawal reactions and no reported cases of dependence. Reports of intentional overdose of pemoline are minimal, with no reports involving abuse via the intravenous route.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION: Pemoline is an amphetamine type psychostimulant drug.Pemoline is used to treat narcolepsy and hyperkinetic states in children as an adjunct to psychological, educational and social measures for amphetamine, dextroamphetamine and ethylphenidate. Misuse: Performance enhancement and relief of fatigue. Abuse: Abuse either orally or by injection is extremely common. HUMAN EXPOSURE: Main risks and target organs: Acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension and cardiovascular collapse. High risk of dependency and abuse. Summary of clinical effects: Cardiovascular: Palpitation, chest pain, tachycardia, arrhythmias and hypertension are common; cardiovascular collapse can occur in severe poisoning. Myocardial ischemia, infarction and ventricular dysfunction are described. Central Nervous System (CNS): Stimulation of CNS, tremor, restlessness, agitation, insomnia, increased motor activity, headache, convulsions, coma and hyperreflexia are described. Stroke and cerebral vasculitis have been observed. Gastrointestinal: Vomiting, diarrhea and cramps may occur. Genitourinary: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. Renal failure can occur secondary to dehydration or rhabdomyolysis. Renal ischemia may be noted. Dermatologic: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Endocrine: Transient hyperthyroxinemia may be noted. Metabolism: Increased metabolic and muscular activity may result in hyperventilation and hyperthermia. Weight loss is common with chronic use. Fluid/Electrolyte: Hypo- and hyperkalemia have been reported. Dehydration is common. Musculoskeletal: Fasciculations and rigidity may be noted. Psychiatric: Agitation, confusion, mood elevation, increased wakefulness, talkativeness, irritability and panic attacks are typical. Chronic abuse can cause delusions and paranoia. A withdrawal syndrome occurs after abrupt cessation following chronic use. Routes of exposure: Oral: Readily absorbed from the gastro-intestinal tract and buccal mucosa. It is resistant to metabolism by monoamine oxidase. Inhalation: Rapidly absorbed by inhalation and is abused by this route. Parenteral: Frequent route of entry in abuse situations. Absorption by route of exposure: Amphetamine is rapidly absorbed after oral ingestion. Peak plasma levels occur within 1 to 3 hours, varying with the degree of physical activity and the amount of food in the stomach. Absorption is usually complete by 4 to 6 hours. Sustained release preparations are available as resin-bound, rather than soluble, salts. These compounds display reduced peak blood levels compared with standard amphetamine preparations, but total amount absorbed and time to peak levels remain similar. Distribution by route of exposure: Concentrated in the kidney, lungs, cerebrospinal fluid and brain. They are highly lipid soluble and readily cross the blood-brain barrier. Protein binding and volume of distribution varies widely, but the average volume of distribution is 5 L/kg body weight. Biological half-life by route of exposure: Under normal conditions, about 30% is excreted unchanged in the urine but this excretion is highly variable and is dependent on urinary pH. When the urinary pH is acidic (pH 5.5 to 6.0), elimination is predominantly by urinary excretion with approximately 60% of a dose being excreted unchanged by the kidney within 48 hours. When the urinary pH is alkaline (pH 7.5 to 8.0), elimination is predominantly by deamination (less than 7% excreted unchanged in the urine); the half-life ranging from 16 to 31 hours. Metabolism: The major metabolic pathway for amphetamine involves deamination by cytochrome P450 to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidized to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation. Hydroxylation produces an active metabolite, O-hyroxynorephedrine, which acts as a false neurotransmitter and may account for some drug effect, especially in chronic users. Elimination and excretion: Normally 5 to 30% of a therapeutic dose is excreted unchanged in the urine by 24 hours, but the actual amount of urinary excretion and metabolism is highly pH dependent. Mode of action: Appears to exert most or all of its effect in the CNS by causing release of biogenic amines, especialy norepinephrine and dopamine, from storage sites in nerve terminals. It may also slow down catecholamine metabolism by inhibiting monoamine oxidase. Toxicity: Adults: The toxic dose varies considerably due to individual variations and the development of tolerance. Children: Children appear to be more susceptible than adults and are less likely to have developed tolerance. Teratogenicity: Amphetamine type compounds generally do not appear to be human teratogens. Mild withdrawal symptoms may be observed in the newborn, but the few studies of infant follow up have not shown long term sequelae, although more studies of this nature are needed. Illicit maternal use or abuse presents a significant risk to the fetus and newborn, including intrauterine growth retardation, premature delivery and the potential for increased maternal, fetal and neonatal morbidity. These poor outcomes are probably multifactorial in origin, involving multiple drug use, life-styles and poor maternal health. However, cerebral injuries occurring in newborns exposed in utero appear to be directly related to the vasoconstrictive properties. Intelligence, psychological function, growth, and physical health were all within the normal range at eight years, but those children exposed throughout pregnancy tended to be more aggressive. Interactions: Acetazolamide: administration may increase serum concentration. Alcohol: may increase serum concentration. Ascorbic acid: lowering urinary pH, may enhance excretion. Furazolidone: May induce a hypertensive response in patients taking furazolidone. Guanethidine: Inhibits the antihypertensive response to guanethidine. Haloperidol: limited evidence indicates that haloperidol may inhibit the effects but the clinical importance of this interaction is not established. Lithium carbonate: isolated case reports indicate that lithium may inhibit the effects. Monoamine oxidase inhibitor: severe hypertensive reactions have followed the administration to patients taking monoamine oxidase inhibitors. Noradrenaline: abuse may enhance the pressor response to noradrenaline. Phenothiazines: may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect. Sodium bicarbonate: large doses of sodium bicarbonate inhibit the elimination, thus increasing the Tricyclic antidepressants: theoretically increases the effect, but clinical evidence is lacking. Clinical effects: Acute poisoning: Ingestion: Effects are most marked on the central nervous system, cardiovascular system, and muscles. The triad of hyperactivity, hyperpyrexia, and hypertension is characteristic of acute overdosage. Agitation, confusion, headache, delirium, and hallucination, can be followed by coma, intracranial hemorrhage, stroke, and death. Chest pain, palpitation, hypertension, tachycardia, atrial and ventricular arrhythmia, and myocardial infarction can occur. Muscle contraction, bruxism (jaw-grinding), trismus (jaw clenching), fasciculation, rhabdomyolysis, are seen leading to renal failure; and flushing, sweating, and hyperpyrexia can all occur. Hyperpyrexia can cause disseminated intravascular coagulation. Inhalation: The clinical effects are similar to those after ingestion, but occur more rapidly. Parenteral exposure: Intravenous injection is a common mode of administration by abusers. The euphoria produced is more intense, leading to a rush or flash which is compared to sexual orgasm. Other clinical effects are similar to those observed after ingestion, but occur more rapidly. Chronic poisoning: Ingestion: Tolerance to the euphoric effects and CNS stimulation induced by such drugs develops rapidly, leading abusers to use larger and larger amounts to attain and sustain the desired affect. Habitual use or chronic abuse usually results in toxic psychosis classically characterized by paranoia, delusions and hallucinations, which are usually visual, tactile or olfactory in nature, in contrast to the typical auditory hallucinations of schizophrenia. The individual may act on the delusions, resulting in bizarre violent behavior, hostility and aggression, sometimes leading to suicidal or homicidal actions. Dyskinesia, compulsive behavior and impaired performance are common in chronic abusers. The chronic abuser presents as a restless, garrulous, tremulous individual who is suspicious and anxious. Course, prognosis, cause of death: Symptoms and signs give a clinical guide to the severity of intoxication as follows: Mild toxicity: restlessness, irritability, insomnia, tremor, hyperreflexia, sweating, dilated pupils, flushing; Moderate toxicity: hyperactivity, confusion, hypertension, tachypnea, tachycardia, mild fever, sweating; Severe toxicity: delirium, mania, self-injury, marked hypertension, tachycardia, arrhythmia, hyperpyrexia, convulsion, coma, circulatory collapse. Death can be due to intracranial hemorrhage, acute heart failure or arrhythmia, hyperpyrexia, rhabdomyolysis and consequent hyperkalemia or renal failure, and to violence related to the psychiatric effects. Systematic description of clinical effects: Cardiovascular: Cardiovascular symptoms of acute poisoning include palpitation and chest pain. Tachycardia and hypertension are common. One third of patients had a blood pressure greater than 140/90 mmHg, and nearly two-thirds had a pulse rate above 100 beats per minute. Severe poisoning can cause acute myocardial ischemia, myocardial infarction, and left ventricular failure. These probably result from vasospasm, perhaps at sites of existing atherosclerosis. In at least one case, thrombus was demonstrated initially. Chronic oral abuse can cause a chronic cardiomyopathy; an acute cardiomyopathy has also been described. Hypertensive stroke is a well recognized complication of poisoning. Intra-arterial injection can cause severe burning pain, vasospasm, and gangrene. Respiratory: Pulmonary fibrosis, right ventricular hypertrophy and pulmonary hypertension are frequently found at post-mortem examination. Pulmonary function tests usually are normal except for the carbon monoxide diffusing capacity. Respiratory complications are sometimes caused by fillers or adulterants used in injections by chronic inhalation abusers. These can cause multiple microemboli to the lung, which can lead to restrictive lung disease. Pneumomediastinum has been reported after inhalation. Neurological: Central nervous system (CNS): Main symptoms include agitation, confusion, delirium, hallucinations, dizziness, dyskinesia, hyperactivity, muscle fasciculation and rigidity, rigors, tics, tremors, seizures and coma. Both occlusive and hemorrhagic strokes have been reported after abuse. Twenty-one of 73 drug using young persons with stroke had taken amphetamine, of whom six had documented intracerebral hemorrhage and two had subarachnoid hemorrhage. Patients with underlying arteriovenous malformations may be at particular risk. Stroke can occur after oral, intravenous, or nasal administration. Severe headache beginning within minutes of ingestion is usually the first symptom. In more than half the cases, hypertension which is sometimes extreme, accompanies other symptoms. A Cerebral vasculitis has also been observed. Dystonia and dyskinesia can occur, even with therapeutic dosages. Psychiatric effects, particularly euphoria and excitement, are the motives for abuse. Paranoia and a psychiatric syndrome indistinguishable from schizophrenia are sequelae of chronic use. Autonomic nervous system: Stimulation of alpha-adrenergic receptors produces mydriasis, increased metabolic rate, diaphoresis, increased sphincter tone, peripheral vasoconstriction and decreased gastrointestinal motility. Stimulation of ß-adrenergic receptors produces increased heart rate and contractility, increased automaticity and dilatation of bronchioles. Skeletal and smooth muscle: Myalgia, muscle tenderness, muscle contractions, and rhabdomyolysis, leading to fever, circulatory collapse, and myoglobinuric renal failure, can occur. Gastrointestinal: Most common symptoms are nausea, vomiting, diarrhea, and abdominal cramps. Anorexia may be severe. Epigastric pain and hematemesis have been described after intravenous use. A case of ischemic colitis with normal mesenteric arteriography in a patient taking dexamphetamine has been described. Hepatic: Hepatitis and fatal acute hepatic necrosis have been described. Urinary Renal: Renal failure, secondary to dehydration or rhabdomyolysis may be observed.Other: Increased bladder sphincter tone may cause dysuria, hesitancy and acute urinary retention. This effect may be a direct result of peripheral alpha-agonist activity. Spontaneous rupture of the bladder has been described in a young woman who took alcohol and an amphetamine containing diet tablet. Endocrine and reproductive systems: Transient hyperthyroxinemia may result from heavy amphetamine use. Dermatological: Skin is usually pale and diaphoretic, but mucous membranes appear dry. Chronic users may display skin lesion, abscesses, ulcers, cellulitis or necrotising angiitis due to physical insult to skin, or dermatologic signs of dietary deficiencies, e.g. cheilosis, purpura. Eye, ear, nose, throat: local effects: Mydriasis may be noted. Diffuse hair loss may be noted and chronic users may display signs of dietary deficiencies. Hematological: Disseminated intravascular coagulation is an important consequence of severe poisoning. Idiopathic thrombocytopenic purpura may occur. Fluid and electrolyte disturbance: Increase metabolic and muscular activity may result in dehydration. Special risks: A case report describes a normal female infant born to mother who took dexamphetamine for narcolepsy throughout pregnancy. Breast-feeding: Amphetamine is passed into breast milk and measurable amounts can be detected in breast-fed infant's urine. Therefore lactating mothers are advised not to take or use these drugs. Other: Withdrawal syndrome: Abrupt discontinuance following chronic use is characterized by apathy, depression, lethargy, anxiety and sleep disturbances. Myalgias, abdominal pain, voracious appetite and a profound depression with suicidal tendencies may complicate the immediate post-withdrawal period and peak in 2 to 3 days. To relieve these symptoms, the user will often return to use more, often at increasing doses due to the tolerance which is readily established. Thus a cycle of use withdrawal use is established. Physical effects here are not life threatening but can lead to a stuporose state; the associated depression can lead to suicide. It may take up to eight weeks for suppressed REM (rapid eye movement) sleep to return to normal. Overamped: When the intravenous dosage is increased too rapidly the individual develops a peculiar condition referred to as overamped: in which he or she is conscious but unable to speak or move. Elevated blood pressure, temperature and pulse as well as chest distress occurs in this setting. Death from overdose in tolerant individuals is infrequent.
International Programme on Chemical Safety; Poisons Information Monograph: Pemoline (PIM 940) (1998) Available from, as of December 6, 2005: https://www.inchem.org/pages/pims.html

12.1.2 Drug Induced Liver Injury

Compound
pemoline
DILI Annotation
Most-DILI-Concern
Severity Grade
8
Label Section
Withdrawn
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

12.1.3 Interactions

If pemoline is administered concomitantly with other drugs, especially those with CNS activity, the patient should be monitored carefully. Decreased seizure threshold has been reported in patients receiving pemoline concomitantly with anticonvulsants.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1310
... Pemoline causes toxic liver damage in children. The severity of the damage is highly variable, and its onset may be late in the course of treatment. Pemoline and methylphenidate may act synergistically to cause liver damage. The levels of serum aminotransferases should be monitored throughout treatment with these agents.
Marotta PJ et al; J Pediatr 132 (5): 894-7 (1998)

12.1.4 Antidote and Emergency Treatment

Treatment of overdose is similar to that for other CNS stimulants. The patient should have IV access established along with frequent monitoring of vital signs and oxygen saturation.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 878
Decontamination: Activated charcoal should be administered to patients with recent ingestions and a protected airway.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 878
Antidotes: There are no specific antidote or antagonist agent for pemoline toxicity.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 878
Supportive Care: Seizure precautions should be observed. A benzodiazepine (diazepam or lorazepam) is the drug of choice for treatment of agitation, tachycardia, hypertension, involuntary movements, or seizures. Aggressive cooling measures should be undertaken for hyperpyrexia. Hypertensive crisis not responding to benzodiazepines may be treated with sodium nitroprusside.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 879

12.1.5 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Pemoline overdose may produce hyperadrenergic effects including agitation, sinus tachycardia, hypertension, hyperpyrexia, mydriasis, and seizures. Acute choreoathetoid movements and hallucinations have also been reported after overdose. In children, choreoathetosis may be the predominant effect and difficult to control. These movements may last up to 24 hours despite treatment with benzodiazepines. Elevated creatine kinase indicating rhabdomyolysis may occur secondary to muscle hypertonicity or seizure activity. The onset of symptoms is usually within 6 hours and may last for 48 hours.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 878
/SIGNS AND SYMPTOMS/ Large doses of pemoline may cause tachycardia. Rash has occurred in patients receiving the drug, and there have been rare reports of aplastic anemia. Pemoline therapy has been associated with elevated serum prostatic acid phosphatase concentrations and prostatic enlargement in a geriatric male patient; the serum prostatic acid phosphatase concentration returned to normal values following discontinuance of the drug and increased again on rechallenge.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
/SIGNS AND SYMPTOMS/ Ingestion of high doses of pemoline by drug abusers has been associated with excitement, restlessness, transient psychotic symptoms (eg, paranoid ideation, hallucinations), and aggressive and disorganized behavior. Irritability, mental depression, and a craving for the drug have occurred when pemoline was abruptly discontinued following excessive use.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
/SIGNS AND SYMPTOMS/ Signs and symptoms of acute overdosage, resulting principally from overstimulation of the central nervous system and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, hypertension and mydriasis.
FDA; Center for Drug Evaluation and Research; Label Information for Cylert (Pemoline) (Last updated December 2002). Available from, as of January 15, 2008: https://www.fda.gov/cder/foi/label/2003/016832s022_017703s018lbl.pdf
For more Human Toxicity Excerpts (Complete) data for PEMOLINE (20 total), please visit the HSDB record page.

12.1.6 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Studies in rats receiving pemoline dosages up to 150 mg/kg daily for 18 months have not revealed evidence of carcinogenicity.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in rats and rabbits using pemoline dosages of 18.75 and 37.5 mg/kg daily have not revealed evidence of harm to the fetus; however, in rats, decreased postnatal survival of offspring occurred at both dosages and increased incidence of stillbirth and cannibalization occurred at the higher dosage.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in male and female rats receiving pemoline dosages of 18.75 and 37.5 mg/kg daily have not revealed evidence of impaired fertility.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309
/LABORATORY ANIMALS: Neurotoxicity/ Acute administration of high doses of amphetamine or pemoline to rats produces transient self injurious behavior which is accompanied by severe deterioration of the behavioral repertoire. Repeated sc administration of pemoline to rats produces a high incidence of self injurious behavior without the dramatic behavioral changes produced by high doses of oral pemoline. Repeated pemoline increased locomotions and rears and produced intermittent stereotyped sniffing and licking/biting. However, the animals were still able to eat, drink, sleep and groom. Hotplate tests provided no evidence for analgesia. Because self injurious behavior is often associated with human developmental disorders, the effects of repeated sc administration of pemoline to weanling rats was also investigated. Sc injections every 12 hr produced a high rate of self injurious behavior in weanling rats.
Mueller K et al; Pharmacol Biochem Behav 25 (5): 933-8 (1986)
For more Non-Human Toxicity Excerpts (Complete) data for PEMOLINE (6 total), please visit the HSDB record page.

12.1.7 Non-Human Toxicity Values

LD50 Rat oral 436 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2075
LD50 Mouse oral 375 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2075
LD50 Mouse ip 365 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 2075

12.1.8 Populations at Special Risk

Pemoline is contraindicated in patients with known hypersensitivity or idiosyncrasy to the drug and in patients with impaired hepatic function.
McEvoy, G.K. (ed.). American Hospital Formulary Service - Drug Information 92. Bethesda, MD: American Society of Hospital Pharmacists, Inc., 1992 (Plus Supplements 1992)., p. 1309

12.1.9 Protein Binding

Approximately 50% (bound to plasma proteins).

12.2 Ecological Information

12.2.1 Environmental Water Concentrations

While data specific to pemoline were not located(SRC, 2008), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).
(1) Heberer T; Tox Lett 131: 5-17 (2002)
(2) Koplin DW et al; Environ Sci Toxicol 36: 1202-211 (2002)

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 Chemical Co-Occurrences in Patents

15.3 Chemical-Disease Co-Occurrences in Patents

15.4 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Drug-Food Interactions

  • Avoid alcohol.
  • Limit caffeine intake.
  • Take with or without food. Food does not significantly affect absorption.

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 WHO ATC Classification System

19.5 ChEMBL Target Tree

19.6 UN GHS Classification

19.7 Drug Enforcement Administration (DEA) Classification

19.8 NORMAN Suspect List Exchange Classification

19.9 EPA DSSTox Classification

19.10 LOTUS Tree

19.11 MolGenie Organic Chemistry Ontology

20 Information Sources

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  17. Therapeutic Target Database (TTD)
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  19. Drugs@FDA
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    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  20. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Pemoline
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  21. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. Human Metabolome Database (HMDB)
    LICENSE
    HMDB is offered to the public as a freely available resource. Use and re-distribution of the data, in whole or in part, for commercial purposes requires explicit permission of the authors and explicit acknowledgment of the source material (HMDB) and the original publication (see the HMDB citing page). We ask that users who download significant portions of the database cite the HMDB paper in any resulting publications.
    http://www.hmdb.ca/citing
  23. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  24. Japan Chemical Substance Dictionary (Nikkaji)
  25. 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
  26. Metabolomics Workbench
  27. SpectraBase
    2-imino-5-phenyl-4-oxazolidinone
    https://spectrabase.com/spectrum/GeVOYUg4GX0
  28. NMRShiftDB
  29. PharmGKB
    LICENSE
    PharmGKB data are subject to the Creative Commons Attribution-ShareALike 4.0 license (https://creativecommons.org/licenses/by-sa/4.0/).
    https://www.pharmgkb.org/page/policies
  30. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  31. Springer Nature
  32. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  33. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  34. Wikidata
  35. Wikipedia
  36. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
    Central Nervous System Stimulants
    https://www.ncbi.nlm.nih.gov/mesh/68000697
  37. PubChem
  38. GHS Classification (UNECE)
  39. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  40. NCBI
CONTENTS