Pyrovalerone

Recommendation (from TRS)

Substance identification
Pyrovalerone (INN, CAS 3563-49-3) is chemically 4’-methyl-2-(1-pyrrolidinyl)valerophenone. There is one chiral carbon in the molecule, so that two stereocisomeric forms and one racemate are possible.

WHO review history
A notification (DND 411/172) WHO, DND 421/12(1-35/36) and note verbale (NAR/CL.11/1986) from the Government of the United States of America concerning descheduling of pyrovalerone have been transmitted to the Director-General of WHO pursuant to Article 2, Paragraph 7 of the Convention on Psychotropic Substances, 1971. Pyrovalerone is at present controlled under Schedule IV of this Convention. It was last reviewed at the twentysecond meeting of the Expert Committee on Drug Dependence (12).

Similarity to known substances and effects on the CNS
Pyrovalerone is believed to be a potent inhibitor of norepinephrine uptake, but no data more recent than those reported in 1978 are available concerning its actions at various receptors or its pharmacological profile in humans.

Dependence potential
The Expert Committee was unable to find any results of experimental anima! or human studies on the dependence potential of pyrovalerone. Clinical observation of abusers of the drug (see below) indicates that intravenously used pyrovalerone produces amfetamine-like stimulation, tolerance and psychological dependence.

Actual abuse and or/evidence of likelihood of abuse
In 1975, about 200 cases of intravenous abuse of pyrovalerone tablets were reported in France in individuals who had previously been heroin and/or amfetamine abusers. Thrombophlebitis was observed in nearly all of these cases. Pyrovalerone was withdrawn from the market in France and Switzerland, but is still available in Luxembourg. Despite efforts to obtain relevant information from the manufacturer, none was received. No illicit traffic or illicit manufacture of pyrovalerone has been reported recently.

Therapeutic usefulness
Pyrovalerone has been used medically to treat asthma and reactive depressive states. It is available in very few countries.

Recommendation
On the basis of the previously available data. concerning its pharmacological profile, dependence potential and actual abuse, the Committee again rated the likelihood of abuse of pyrovalerone as moderate and the therapeutic usefulness as low. Consistent with the extremely limited availability of the drug, the public health and social problems currently associated with it have been found to be few and not serious. However, no new data were presented to suggest that the public health problems previously associated with pyrovalerone are not likely to re-emerge. The Committee recommended retaining pyrovalerone under international control in Schedule IV of the Convention on Psychotropic Substances, 1971.

ECDD Recommendation

No change in scheduling