Stereoselective neurochemical, behavioral, and cardiovascular effects of α‐pyrrolidinovalerophenone enantiomers in male rats

The synthetic cathinone α‐pyrrolidinovalerophenone (α‐PVP) continues to be abused despite being banned by regulatory agencies. The abused formulation of α‐PVP is a racemic mixture consisting of two enantiomers, S‐α‐PVP and R‐α‐PVP. In this study, we investigated the neurochemical, behavioral, and cardiovascular effects of racemic α‐PVP and its enantiomers in male rats. Racemic α‐PVP blocked the uptake of both dopamine and norepinephrine ex vivo, but did not block the uptake of serotonin (5‐HT), at their respective transporters. S‐α‐PVP was slightly more potent than racemic α‐PVP, while R‐α‐PVP was 10 to 20 times less potent at blocking dopamine and norepinephrine uptake. In microdialysis studies, racemic and S‐α‐PVP increased extracellular dopamine levels in the nucleus accumbens, but not levels of 5‐HT. Racemic and S‐α‐PVP also increased locomotor activity. When tested at the same doses, S‐α‐PVP produced larger effects than racemic α‐PVP. R‐α‐PVP also increased extracellular dopamine levels and locomotor activity, but only at 30 times higher doses than S‐α‐PVP. Racemic and S‐α‐PVP were self‐administered by rats at 0.03 mg/kg/injection, whereas R‐α‐PVP was self‐administered at a 10 times higher dose. Dose‐effect determinations following acquisition suggested that R‐α‐PVP was at least 30 times less potent than S‐α‐PVP. Finally, racemic and S‐α‐PVP increased blood pressure and heart rate at doses approximately 30 times less than was required for R‐α‐PVP to produce similar effects. These results show that the neurochemical, behavioral, and cardiovascular effects of racemic α‐PVP most likely reflect the actions of S isomer. Effects of racemic α‐PVP and its enantiomers on dose‐effect functions for (A) blood pressure and (B) heart rate. Rats were implanted with telemetry transmitters that sampled blood pressure and heart rate every 1 minute for 3 hours. Data are expressed as mean ± standard error of the mean (SEM) for n = 5 to 7 rats/group for the entire 3‐hour sampling period. Solid symbols represent significant difference from the respective saline (P