Distinguishing the behavioral potencies of α-pyrrolidino-phenone cathinone stimulants

The α-pyrrolidino-phenone cathinone stimulants first came to widespread attention because of bizarre behavior consequent to the use of α-pyrrolidinopentiophenone (α-PVP, “flakka”) reported in the popular press. As with other designer drugs, diversification of cathiones has been driven by desireable subjective effects, but also by attempts to stay ahead of legal controls of specific molecules. The α-pyrrolidinohexiophenone (α-PHP) and α-pyrrolidinopropiophenone (α-PPP) compounds have been relatively under-investigated relative to α-PVP and provide a key opportunity to also investigate structure-activity relationships, i.e., how the extension of the alpha carbon chain may affect potency or efficacy. Male and female rats were used to contrast the effects of α-PHP and α-PPP with those of α-PVP in altering wheel activity and effects on spontaneous locomotion and body temperature were assessed in female rats. The α-PHP and α-PVP compounds (5, 10 mg/kg, i.p.) suppressed wheel activity in female and male rats, whereas α-PPP was only effective in female rats. Inhalation of α-PHP or α-PVP by female rats suppressed wheel activity for an abbreviated duration, compared with the injection route. Spontaneous activity was increased in a dose-dependent manner by all three compounds in female rats, and a small decrements in body temperature were observed after the highest dose of all three compounds. These data show that all three of the α-pyrrolidino-phenone cathinones exhibit significant stimulant-like activity in both male and female rats. Differences were minor and were mostly in potency and the duration of activity. Abuse liability is therefore likely to be equivalent for all three pyrrolidino-phenones.