Pharmacological profile, phase I metabolism, and excretion time profile of the new synthetic cathinone 3,4‐Pr‐PipVP

Abstract

Abstract1‐(2,3‐Dihydro‐1H‐inden‐5‐yl)‐2‐(piperidin‐1‐yl)pentan‐1‐one (3,4‐Pr‐PipVP), a novel synthetic cathinone (SCat), was first identified in 2022 in Germany. The product was marketed as 1‐(bicyclo[4.2.0]octa‐1,3,5‐trien‐3‐yl)‐2‐(pyrrolidin‐1‐yl)pentan‐1‐one (3,4‐EtPV), a substance not covered by the German New Psychoactive Substances Act (NpSG). Although originally intended to be an exploratory new synthetic cathinone containing the novel bicyclo[4.2.0]octatrienyl function, the compound was subsequently confirmed to contain an indanyl ring system scheduled under generic legislation like the NpSG. However, it is one of only a few marketed SCats carrying a piperidine ring. Inhibition experiments involving norepinephrine, dopamine, and serotonin transporters showed that 3,4‐Pr‐PipVP was a low potency blocker at all three monoamine transporters compared to related substances such as MDPV. Additionally, pharmacokinetic data were collected from pooled human liver microsomes incubations and from the analysis of authentic urine samples received after oral administration of 5 mg 3,4‐Pr‐PipVP hydrochloride. Phase I metabolites were tentatively identified in vitro and in vivo using liquid chromatography−time‐of‐flight mass spectrometry. Main metabolites were formed by metabolic reduction of the carbonyl function with and without additional hydroxylations at the propylene bridge of the molecule. Keto‐reduced H2–3,4‐Pr‐PipVP and H2‐piperidine‐OH‐3,4‐Pr‐PipVP as well as aryl‐OH‐3,4‐Pr‐PipVP, and indanyl‐OH‐piperidine‐OH‐3,4‐Pr‐PipVP are suggested as most suitable biomarkers for the detection of 3,4‐Pr‐PipVP since they were detected for much longer than the parent compound. 3,4‐Pr‐PipVP could be detected for up to 21 h whereas its metabolites were detectable for up to about 4 days.

Structure–Activity Relationship of Synthetic Cathinones: An Updated Review

“…150 Furthermore, and in contrast to its nonsubstituted analogue α-piperidinevalerophenone (α-PpVp), 3,4-propylene-2-(1-piperidinyl)valerophenone (3,4-Pr-PipVP) which contains a propylene bridge, results in equal potency at inhibiting DAT vs SERT. 151 The introduction of bulkier substituents in different positions of the aromatic ring also plays a role in the releasing properties of synthetic cathinones. Walther and colleagues demonstrated that bulkier substituent at the metaor para-position of MCAT results in decreased DAT release potency.…”