Methyl (2S)-2-{[1-(5-fluoropentyl)-1H-indole-3-carbonyl]amino}-3,3-dimethylbutanoate

Year(s) and type of review / ECDD meetings
Drug Class
Technical information (most recent pre-review / critical review report)

Recommendation (from TRS)

Substance identification
Alpha-PHP (alpha-pyrrolidinohexanophone; 1-phenyl-2-(pyrrolidine-1-yl) hexan-1-one) is a synthetic cathinone that was developed and patented in 1967 but never marketed. In its pure form, alpha-PHP is usually a crystalline solid or powder.

WHO review history
Alpha-PHP has not been reviewed previously. A critical review was proposed on the basis of information brought to WHO’s attention that alpha-PHP is manufactured clandestinely, poses a risk to public health and society and has no therapeutic use recognized by any Party.

Similarity to known substances and effects on the central nervous system
Alpha-PHP enhances the activity of the neurotransmitter dopamine by blocking re-uptake. It has a similar but lesser effect on the neurotransmitter noradrenaline. It shares similar molecular mechanisms and functional properties with other psychostimulants that are currently controlled under the Convention on Psychotropic Substances of 1971.

In humans, alpha-PHP causes central nervous system stimulation similar to other psychostimulants, with effects such as tremor, sweating, psychosis, paranoia, hallucinations, agitation, anxiety, hypertension, tachycardia, seizures and unconsciousness. Other reported adverse effects include depressed mood, irritability, headache, insomnia and nausea. Consistent with the effects of other psychostimulants, alpha-PHP is an anorexic, has reinforcing properties and induces craving. Because of its extended half-life, long-lasting psychotic symptoms have been reported. Users report a range of effects that are consistent with the stimulant activity of the drug.

Dependence potential
No controlled experimental studies of the dependence potential of alpha-PHP in humans or animal models have been reported. Its mechanism of action, particularly the effect on dopamine, suggests, however, that it is highly likely to produce a state of dependence similar to amphetamine and other psychostimulants.

Actual abuse and/or evidence of likelihood of abuse
In drug discrimination tests in animals, alpha-PHP was readily self-administered, with greater reinforcing effects than some other cathinones, suggesting that it has high abuse liability. In drug discrimination assays in animals predictive of subjective effects in humans, alpha-PHP showed effects similar to those of cocaine and methamphetamine.

Alpha-PHP has been identified on the illicit drug market, and hundreds of seizures have been reported.

In reports of fatal and non-fatal intoxications, alpha-PHP has been detected in biological fluids, sometimes as the only drug present or as the drug that made the most significant contribution to the person’s condition.

Therapeutic usefulness
alpha-PHP is not known to have any therapeutic use.

Alpha-PHP (1-phenyl-2-(pyrrolidine-1-yl)hexan-1-one; also known as alpha- pyrrolidinohexanophenone), is a synthetic cathinone with effects similar to those of other synthetic cathinones and of other psychostimulants such as amphetamine, that are listed under Schedule II of the Convention on Psychotropic Substances of 1971. Through its mechanism of action and effects, alpha-PHP can stimulate the central nervous system and produce a state of dependence. There is evidence that its abuse constitutes a public health and social problem. It has no therapeutic use.

■ Recommendation: The Committee recommended that alpha-PHP (1-phenyl-2-(pyrrolidine -1-yl) hexan-1-one) be added to Schedule II of the 1971 Convention on Psychotropic Substances.

ECDD Recommendation

Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances