Alpha-Pyrrolidinovalerophenone

Alternative names
α-PVP, alpha-PVP, α-Pyrrolidinovalerophenone
IUPAC Name

1-Phenyl-2-(pyrrolidin-1-yl)pentan-1-one

Year(s) and type of review / ECDD meetings
Drug Class

Recommendation (from TRS)

Substance identification
Chemically, α-PVP (α-pyrrolidinovalerophenone) is 1-phenyl-2-(pyrrolidin- 1-yl)pentan-1-one. This synthetic cathinone is the desmethyl analogue of pyrovalerone that is listed in Schedule IV of the 1971 United Nations Convention on Psychotropic Substances. α-PVP has two enantiomers and is commonly available as the racemic mixture. α-PVP is closely related to 3′,4′-methylenedioxypyrovalerone (MDPV) that has recently been placed in Schedule II of the UN Convention on Psychotropic Substances (1971).

Previous review
α-PVP has not been previously reviewed by the Committee. A direct critical review was proposed based on information brought to WHO’s attention that α-PVP is clandestinely manufactured, poses a risk to public health and society, and has no recognized therapeutic use by any Party.

Similarity to known substances and effects on the central nervous system
α-PVP is a potent blocker at the dopamine transporter (DAT) and a moderate blocker at the norepinephrine transporter (NET) with negligible activity at the serotonin transporter (SERT), similar to some other psychostimulants. In many preclinical procedures it demonstrates a psychostimulant-like profile in which it increases locomotion, produces stereotypies, fully substitutes for the discriminative stimulus effects of cocaine and methamphetamine, decreases intracranial self-stimulation thresholds, produces conditioned place preference and is self-administered.

Dependence potential
Research data using human subjects pertinent to α-PVP’s dependence potential have not been reported. In preclinical studies, behavioural effects induced by α-PVP are comparable to those produced by other psychomotor stimulants such as cocaine, methamphetamine and MDPV, which predict a stimulant-like dependence potential.

Actual abuse and/or evidence of likelihood of abuse
Several of the nonclinical effects of α-PVP predict a likelihood of abuse for α-PVP in that it decreases intracranial self-stimulation thresholds, produces conditioned place preference, and is self-administered. α-PVP has been sold as a "research chemical", "bath salt", "stain remover", "plant food", "plant fertilizer", "insect repellent", and "jewellery cleaner" and in the form of tablets, suppositories, ampoules, and in liquid formulations. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) identified 65 Internet vendors of α-PVP including some presumably based in China, the European Union, India, the Russian Federation and the United States. α-PVP has been associated with both non-fatal and fatal intoxications. Frequently, when analysed, α-PVP is identified in biofluids, accompanied by other abused substances. In cases where α-PVP use has been established unambiguously, neurological, psychiatric and cardiovascular effects consistent with an extensive psychostimulant toxidrome have been observed, which include cardiotoxicity and violent and psychotic behaviour. More than 130 deaths have been associated with α-PVP, and hospitalizations were required among users with non-fatal acute intoxications.

Therapeutic usefulness
There are no known approved medical products containing α-PVP.

Recommendation
The Committee considered that the degree of risk to public health and society associated with the abuse of α-PVP is substantial. Therapeutic usefulness has not been recorded. Its pharmacological effects are similar to methamphetamine and MDPV, psychostimulants listed in Schedule II of the 1971 Convention. The Committee considered that the evidence of its abuse warranted its placement under international control. As per the Guidance on the WHO review of psychoactive substances for international control (4), higher regard was accorded to the substantial public health risk than to the lack of therapeutic usefulness. The Committee recommended that α-PVP be placed in Schedule II of the 1971 Convention.

ECDD Recommendation

Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances