α-PVP
α-Pyrrolidinovalerophenone (α-PVP), also known as α-pyrrolidinopentiophenone , O-2387, β-keto-prolintane, prolintanone, or desmethylpyrovalerone, or colloquially as flakka or gravel, is a synthetic stimulant of the cathinone class developed in the 1960s that has been sold as a designer drug and often consumed for recreational reasons. α-PVP is chemically related to pyrovalerone and is the ketone analog of prolintane.
Use and effects
α-PVP is used by a variety of different routes of administration, including oral, insufflation, injection, vaporization, sublingual, and rectal. The dose range of α-PVP for therapeutic purposes was originally defined as 10 to 50 mg, with a most-suitable dose of 20 mg, whereas the recreational dose range is typically between 10 and 300 mg. The effects of α-PVP onset after 10 minutes, peak after 10 to 40 minutes, and last 2 to 3 hours.
The effects of α-PVP include cocaine-like psychostimulant effects, euphoria, elevated mood, alertness, pleasurable rush, feeling “sped up”, mania-like symptoms, enhanced energy, motivation and productivity, enhanced music enjoyment, mild sexual stimulation, insomnia, paranoia, hallucinations, and increased aggression and violence. In emergency settings, commonly observed effects have included psychosis-like state, agitation, aggression, hallucinations, abnormal heart rate, and vomiting. It also produces sympathomimetic effects, such as increased heart rate and blood pressure.
Pharmacology
| Drug | NET | DAT | SERT | DAT/SERT Ratio |
|---|---|---|---|---|
| ⍺-PVP | 0.02 (0.01‒0.05) | 0.03 (0.02‒0.04) | 279 (209‒372) | >1000 |
| ⍺-PHP | 0.06 (0.03‒0.12) | 0.06 (0.05‒0.08) | 245 (173‒348) | >1000 |
| MDMA | 0.41 (0.33‒0.52) | 13 (11‒16) | 1.6 (1.2‒2.2) | 0.12 (0.08‒0.20) |
| Amphetamine | 0.07 (0.05‒0.1) | 1.3 (0.8‒2.0) | 45 (24‒85) | 35 (12‒106) |
Pharmacodynamics
α-PVP acts as a potent norepinephrine–dopamine reuptake inhibitor (NDRI), similarly to other NDRIs like methylphenidate, cocaine, and methylenedioxypyrovalerone (MDPV). Its 50“},”2”:{“wt”:”half-maximal inhibitory concentration”}},”i”:0}}]}”>half-maximal inhibitory concentration“}]]}”>IC50Tooltip half-maximal inhibitory concentration values have been found to be 14 to 70 nM for norepinephrine reuptake inhibition and 13 to 80 nM for dopamine reuptake inhibition in rat brain synaptosomes and human embryonic kidney 293 (HEK293) cells expressing the monoamine transporters (MATs). In contrast to its effects on catecholamine reuptake, α-PVP has negligible effects on serotonin reuptake.
The drug is much more potent than amphetamine as an NDRI in in vitro, with 46-fold greater potency in terms of dopamine reuptake inhibition and 7-fold greater potency in terms of norepinephrine reuptake inhibition in HEK293 cells. It is one of the most potent dopamine reuptake inhibitors in vitro known.
