Pemoline

2-amino-5-phenyl-1,3-oxazol-4-one

Overview

Pemoline belongs to Stimulants.

Key safety note: Pemoline's defining hazard is idiosyncratic, sometimes fatal liver toxicity.[2][3]
Effects
Subjective effects vary. What a substance feels like depends on dose, individual physiology, mindset, and setting. The points below describe commonly reported effects, not guaranteed, uniform, or desirable outcomes.
  • A gradual, relatively mild stimulant effect, improved wakefulness, attention and concentration, that builds over days to weeks rather than acutely, with less of the sharp 'rush' of amphetamine.
  • Common stimulant side effects: insomnia, reduced appetite and weight loss, raised heart rate and blood pressure, irritability and headache.
  • At high or misused doses: agitation, abnormal involuntary movements (choreoathetosis), and rarely hallucinations or psychosis. The serious, dose-independent risk is liver injury.
Dosing & duration
Harm-reduction note: These are commonly cited reference ranges, not a recommendation or a “safe” dose. Potency, purity, body chemistry, tolerance, and drug combinations vary widely. Start low, go slow, wait for full effects before redosing, and never assume an unknown product matches these figures. Missing data is not evidence of safety.

Oral only, once daily: clinician-prescribed. Figures below are historical clinical ranges, NOT a recreational guide. Pemoline has been withdrawn in most countries because of fatal liver toxicity.. Pemoline was taken once a day by mouth. Its therapeutic effect builds gradually and may not appear until the third or fourth week. There is no safe recreational use: its defining risk is unpredictable, sometimes fatal liver failure that is independent of dose and not reliably prevented by monitoring, which is why it has been withdrawn from most markets.

Dose ranges

ADHD (clinical, historical)

≈18.75–112.5 mg once daily (usual effective ≈56–75 mg)

Onset of therapeutic effect

Gradual: often not until week 3–4

Duration

onset

Peak blood levels ≈2–4 h, clinical benefit builds over weeks

total

Once-daily dosing (half-life ≈7–12 h in adults)

after effects

Insomnia/appetite suppression may persist. Liver injury can appear at any time

Chemical & Physical Properties
FormulaC9H8N2O2
Molar mass176.17 g/mol
StateSolid
Melting point256 dec °C
Boiling pointNot reported
DensityNot reported
Vapor pressureNot reported
pKa10.5
LogP0.7
SolubilityPractically insol in ether, acetone, dil hydrochloric acid. Sol in propylene glycol (1%) and hot alcohol
Refractive indexNot reported
Identifiers & Synonyms
CAS2152-34-3
CAS (enantiomer)
PubChem CID4723
InChIKeyNRNCYVBFPDDJNE-UHFFFAOYSA-N
InChIInChI=1S/C9H8N2O2/c10-9-11-8(12)7(13-9)6-4-2-1-3-5-6/h1-5,7H,(H2,10,11,12)
SMILESC1=CC=C(C=C1)C2C(=O)N=C(O2)N

Synonyms

  • Cylert
Pharmacodynamics & Biochemistry

Pemoline (Cylert) is a central nervous system stimulant of the 4-oxazolidinone class: structurally unrelated to the amphetamines or methylphenidate. It appears to act mainly by enhancing dopaminergic neurotransmission: it is described as a dopamine reuptake inhibitor and releasing agent (an indirect dopamine agonist), raising dopamine signalling in the brain. Unusually for a stimulant it produces little peripheral or central noradrenergic effect, which historically gave it a reputation for being less overtly sympathomimetic than amphetamine. Its precise mechanism is poorly characterised, and no reliable quantitative binding constants (Kᵢ/IC50 at the dopamine, noradrenaline or serotonin transporters) have been established for it, so the binding-affinity table is left empty rather than filled with unverified numbers. Its onset is notably slow: the therapeutic effect in ADHD builds gradually and may not be apparent until the third or fourth week of treatment, consistent with an action that is not simply acute transporter blockade. Pemoline is well absorbed orally, reaching peak blood levels at ≈2–4 h, with a half-life of about 7–12 hours in adults (shorter in children), allowing once-daily dosing. It is metabolised in the liver (to a conjugate, pemoline dione and mandelic acid), with roughly half the dose excreted unchanged in the urine.

Biological targets

  • DAT
Pharmacokinetics
BioavailabilityOral, well absorbed
Tmax≈2–4 h
Half-life≈7–12 h (adults, shorter in children)
VdNot reported
Protein bindingLow (~≤50%, reports vary)
MetabolismHepatic (conjugate, pemoline dione, mandelic acid)
ExcretionRenal. ~50% excreted unchanged
Toxicology & Safety
Harm-reduction note: Toxicity and risk depend on dose, route, purity, combinations, setting, and individual health factors. Missing harms should never be interpreted as evidence of safety.

Not reported

Pemoline's defining hazard is idiosyncratic, sometimes fatal liver toxicity. Post-marketing surveillance linked it to acute hepatic failure: at least 21 reported cases of liver failure, of which about 13 ended in death or liver transplantation: occurring unpredictably and not reliably caught by routine liver-function monitoring. This risk led to its withdrawal from the market in the UK (1997) and Canada (1999) and to the withdrawal of Cylert and its generics in the United States (2005). It remains available in only a few countries (e.g. Japan, for narcolepsy). As a stimulant it can also cause insomnia, appetite loss, weight loss, tachycardia, raised blood pressure and irritability, and, at high or misused doses, agitation, abnormal involuntary movements (choreoathetosis) and, rarely, psychosis. It carries some potential for dependence and misuse. Because the liver injury is idiosyncratic and can be rapid, it is generally regarded as a last-line agent where it is used at all.[2][3]

Legal Status
Legal note: Legal status can change over time and may vary by country, region, formulation, analogue status, prescription context, and enforcement practice. Always confirm with current official sources before relying on this section.
Interactions & Contraindications

Drug interactions

Stimulants (amphetamines, cocaine) Additive cardiovascular stimulation (raised heart rate and blood pressure) and agitation with other stimulants or sympathomimetics.[3]
Other hepatotoxic drugs Potentially additive liver injury with other hepatotoxic drugs or alcohol, a particular concern given pemoline's idiosyncratic hepatotoxicity.[2][3]
Drugs that lower the seizure threshold May lower the seizure threshold, so caution with other drugs that do the same or in people with epilepsy.[3]

Contraindications

Kidney or liver impairment pre-existing hepatic impairment or abnormal liver function.[2][3]
Known hypersensitivity to the drug prior hypersensitivity or liver reaction to pemoline.[2]
Cardiovascular disease, hypertension or arrhythmia cardiovascular disease or hypertension, with caution in a history of drug misuse or psychosis.[3]
Usage & Context
  • A once-daily prescription stimulant formerly used for attention-deficit hyperactivity disorder (ADHD) and for narcolepsy / excessive daytime sleepiness, marketed chiefly as Cylert (also Volital, Betanamin and others).
  • Now largely of historical interest: withdrawn from the UK, Canadian and US markets because of fatal hepatotoxicity, and available in only a few countries (notably Japan, for narcolepsy).
  • Occasionally encountered as a stimulant of misuse, but far less so than amphetamine or methylphenidate.
Sources & Evidence

Further Information