Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Pemoline (INN, CAS 2152- 34. 3) exists in two tautomeric forms, 2-amino- 5-phenyl- 2-oxazolin-4-one and 2-imino-5-phenyl- 4-0xazolidinone. It is also known as phenoxazole, phenylisobydantoin and phenylpseudohydantoin: There is-one chiral:carbon atom in the molecule, so that two stereoisomers and one racemate are-possible.
WHO review history
Pemoline was first reviewed at the twenty-second meeting of the Expert Committee on Drug Dependence (12). The view of the Committee at that time was that it was not likely to be associated with significant public health problems; it was therefore not recommended for control. Because of recent reports of significant illicit trafficking in Africa, Europe and South America, pemoline was recommended for re-evaluation and for possible scheduling.
Similarity to known substances and effects on the CNS
Pemoline has been classified pharmacologically as an amfetamine-like, indirect dopaminergic agonist. It increases locomotor activity in a variety of animal species. In humans, it
decreases appetite and produces central stimulant effects. While not similar to amfetamine with respect to some neurochemical mechanisms, its psychotoxic effects can resemble those of that substance. In large doses it can produce motor stimulation, hyperactivity, dyskinesia, seizures, insomnia and hallucinations, and may also aggravate or produce psychosis. Pemoline is metabolized partially to less active metabolites which are excreted as conjugates in the urine. It is not readily soluble in water and is usually administered orally as magnesium pemoline. Pemoline has a less rapid onset of action than amfetamine, and its actions on the central nervous system do not peak until 2-3 hours after oral ingestion.
Dependence potential
Pemoline is not self-administered by rhesus monkeys and does not act as a reinforcer in these animals. Recent studies in nondependent substance abusers demonstrate that its reinforcing properties in humans are quite limited. It is typically not reinforcing or euphoriant at doses of up to 37.5 mg and is toxic and dysphoric at doses of 150mg. At doses of 75 mg it has mild effects on the central nervous system, roughly equivalent to those of 15mg of amfetamine. Its euphoric effects at this dose are significantly less than those observed with 30 mg of amfetamine. In contrast to the value placed on 15 mg of amfetamine, subjects did not view any dose of pemoline as having any monetary value. Since the drug is not readily soluble, parenteral abuse of it is not likely. The dependence potential of pemoline in humans has not been established and the evidence for or against it is not convincing.
Actual abuse and or/evidence of likelihood of abuse
A few isolated case reports of dependence on pemoline have been published. There have also been reports of its abuse from the governments of Belgium, the Federal Republic of Germany, Thailand and the United Kingdom, and a few mentions from hospital emergency rooms have appeared in the reports of the Drug Abuse Warning Network each year. A few cases of pemoline abuse and dependence have been seen each year over the last few years in several psychiatric hospitals in Argentina. Pemoline is marketed illicitly "on the street" in the United Kingdom as "speed", and its use has been suspected in some cases of drugging of athletes and doping of racehorses. During the few years preceding the Committee’s 1985 review of pemoline there had been reports of illicit trafficking in pemoline and two seizures of the drug. In 1985, at its twenty-second meeting, the Expert Committee on Drug Dependence reviewed pemoline in order to determine whether international control was appropriate (/2). At that time, the Committee concluded that "while pemoline has been in use in many countries, the available data do not indicate that the drug has been or is likely to be associated with significant public health problems. It therefore concluded that international control was not necessary. However, since then, there has been a significant increase in the amount of pemoline shipped across national borders and in international illicit trafficking, as judged by seizures of the drug by law enforcement authorities. For example, the number of seizures of pemoline in the United Kingdom increased from 12 (8064 dosage units) in 1985 to 17 (1 818 240 dosage units) in 1987. Seizures have been reported in ten other countries, including the Netherlands; where 6750 kg were seized during April. 1988; this large quantity, which originated in Eastern Europe, was destined for Africa. via Western Europe. Exports of pemoline from one European country to Nigeria increased from 75 million dosage units in 1985 to 146 million in 1986, but fell to 78 million in 1987. There is no apparent legitimate medical use of pemoline in Nigeria and the Nigerian Ministry of Health has not authorized any importation of it. Pemoline exports from another European country increased from 7768 kg in 1985 to 9323 kg in 1986. This pemoline was shipped indirectly to Africa, Asia and South America, and the method of payment and shipment was such as to indicate clearly that the intention was to distribute the drug for non-medical purposes. At present there is very little information on what happens to all this pemoline, and estimates of the resulting public health and social problems must:-remain inferences drawn from the quantities of the drug moving in international non-medical channels. Nevertheless, international traffic is now. of such magnitude as to be difficult to ignore.
Therapeutic usefulness
Pemoline is available for medical use in a number of countries, where it may be indicated in child and adult psychiatry for attention deficit disorders. It has also been tried in geriatrics to treat lethargy and depressive syndromes induced both by medicines and by physical and mental fatigue. In some countries, concerns about abuse and/or severe restrictions on the availability of other amfetamine-like agents have sometimes resulted in a relative increase in the therapeutic use of pemoline.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and documented cases of abuse, the Committee rated the dependence potential of pemoline as low. The apparent demand for the drug for non-medical purposes suggests that more data are required to resolve the discrepancy between laboratory-based estimates of a low abuse liability and the higher abuse liability suggested by the illicit traffic and case reports. Reliable evidence of extensive abuse or of serious public health problems related to the non-medical use of pemoline was not presented to or uncovered by the Committee. However, given the amount of pemoline reported to be moving in international channels, which exceeds what is required to meet any reasonable medical need, serious public health and social problems are assumed to be developing, and are likely to become increasingly obvious if current levels of non-medical use persist. The Committee rated the therapeutic usefulness of pemoline as low to moderate. In the light of this assessment, the Committee recommended scheduling of the drug in Schedule IV of the Convention on Psychotropic Substances, 1971.
Pemoline (INN, CAS 2152- 34. 3) exists in two tautomeric forms, 2-amino- 5-phenyl- 2-oxazolin-4-one and 2-imino-5-phenyl- 4-0xazolidinone. It is also known as phenoxazole, phenylisobydantoin and phenylpseudohydantoin: There is-one chiral:carbon atom in the molecule, so that two stereoisomers and one racemate are-possible.
WHO review history
Pemoline was first reviewed at the twenty-second meeting of the Expert Committee on Drug Dependence (12). The view of the Committee at that time was that it was not likely to be associated with significant public health problems; it was therefore not recommended for control. Because of recent reports of significant illicit trafficking in Africa, Europe and South America, pemoline was recommended for re-evaluation and for possible scheduling.
Similarity to known substances and effects on the CNS
Pemoline has been classified pharmacologically as an amfetamine-like, indirect dopaminergic agonist. It increases locomotor activity in a variety of animal species. In humans, it
decreases appetite and produces central stimulant effects. While not similar to amfetamine with respect to some neurochemical mechanisms, its psychotoxic effects can resemble those of that substance. In large doses it can produce motor stimulation, hyperactivity, dyskinesia, seizures, insomnia and hallucinations, and may also aggravate or produce psychosis. Pemoline is metabolized partially to less active metabolites which are excreted as conjugates in the urine. It is not readily soluble in water and is usually administered orally as magnesium pemoline. Pemoline has a less rapid onset of action than amfetamine, and its actions on the central nervous system do not peak until 2-3 hours after oral ingestion.
Dependence potential
Pemoline is not self-administered by rhesus monkeys and does not act as a reinforcer in these animals. Recent studies in nondependent substance abusers demonstrate that its reinforcing properties in humans are quite limited. It is typically not reinforcing or euphoriant at doses of up to 37.5 mg and is toxic and dysphoric at doses of 150mg. At doses of 75 mg it has mild effects on the central nervous system, roughly equivalent to those of 15mg of amfetamine. Its euphoric effects at this dose are significantly less than those observed with 30 mg of amfetamine. In contrast to the value placed on 15 mg of amfetamine, subjects did not view any dose of pemoline as having any monetary value. Since the drug is not readily soluble, parenteral abuse of it is not likely. The dependence potential of pemoline in humans has not been established and the evidence for or against it is not convincing.
Actual abuse and or/evidence of likelihood of abuse
A few isolated case reports of dependence on pemoline have been published. There have also been reports of its abuse from the governments of Belgium, the Federal Republic of Germany, Thailand and the United Kingdom, and a few mentions from hospital emergency rooms have appeared in the reports of the Drug Abuse Warning Network each year. A few cases of pemoline abuse and dependence have been seen each year over the last few years in several psychiatric hospitals in Argentina. Pemoline is marketed illicitly "on the street" in the United Kingdom as "speed", and its use has been suspected in some cases of drugging of athletes and doping of racehorses. During the few years preceding the Committee’s 1985 review of pemoline there had been reports of illicit trafficking in pemoline and two seizures of the drug. In 1985, at its twenty-second meeting, the Expert Committee on Drug Dependence reviewed pemoline in order to determine whether international control was appropriate (/2). At that time, the Committee concluded that "while pemoline has been in use in many countries, the available data do not indicate that the drug has been or is likely to be associated with significant public health problems. It therefore concluded that international control was not necessary. However, since then, there has been a significant increase in the amount of pemoline shipped across national borders and in international illicit trafficking, as judged by seizures of the drug by law enforcement authorities. For example, the number of seizures of pemoline in the United Kingdom increased from 12 (8064 dosage units) in 1985 to 17 (1 818 240 dosage units) in 1987. Seizures have been reported in ten other countries, including the Netherlands; where 6750 kg were seized during April. 1988; this large quantity, which originated in Eastern Europe, was destined for Africa. via Western Europe. Exports of pemoline from one European country to Nigeria increased from 75 million dosage units in 1985 to 146 million in 1986, but fell to 78 million in 1987. There is no apparent legitimate medical use of pemoline in Nigeria and the Nigerian Ministry of Health has not authorized any importation of it. Pemoline exports from another European country increased from 7768 kg in 1985 to 9323 kg in 1986. This pemoline was shipped indirectly to Africa, Asia and South America, and the method of payment and shipment was such as to indicate clearly that the intention was to distribute the drug for non-medical purposes. At present there is very little information on what happens to all this pemoline, and estimates of the resulting public health and social problems must:-remain inferences drawn from the quantities of the drug moving in international non-medical channels. Nevertheless, international traffic is now. of such magnitude as to be difficult to ignore.
Therapeutic usefulness
Pemoline is available for medical use in a number of countries, where it may be indicated in child and adult psychiatry for attention deficit disorders. It has also been tried in geriatrics to treat lethargy and depressive syndromes induced both by medicines and by physical and mental fatigue. In some countries, concerns about abuse and/or severe restrictions on the availability of other amfetamine-like agents have sometimes resulted in a relative increase in the therapeutic use of pemoline.
Recommendation
On the basis of the available data concerning its pharmacological profile, dependence potential and documented cases of abuse, the Committee rated the dependence potential of pemoline as low. The apparent demand for the drug for non-medical purposes suggests that more data are required to resolve the discrepancy between laboratory-based estimates of a low abuse liability and the higher abuse liability suggested by the illicit traffic and case reports. Reliable evidence of extensive abuse or of serious public health problems related to the non-medical use of pemoline was not presented to or uncovered by the Committee. However, given the amount of pemoline reported to be moving in international channels, which exceeds what is required to meet any reasonable medical need, serious public health and social problems are assumed to be developing, and are likely to become increasingly obvious if current levels of non-medical use persist. The Committee rated the therapeutic usefulness of pemoline as low to moderate. In the light of this assessment, the Committee recommended scheduling of the drug in Schedule IV of the Convention on Psychotropic Substances, 1971.
ECDD Recommendation
Inclusion in Schedule IV of the 1971 Convention on Psychotropic Substances
Link to full TRS
who_trs_775.pdf1.98 MB