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In vitro pharmacology of pipradrol derivatives, 3,4‐methylenedioxypyrovalerone, and naphyrone (1145.3)
Author(s) -
Liechti Matthias,
Simmler Linda,
Rickli Anna,
Hoener Marius
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1145.3
Subject(s) - monoaminergic , pharmacology , dopamine transporter , norepinephrine transporter , chemistry , monoamine neurotransmitter , dopamine , methylphenidate , serotonin , transporter , receptor , medicine , biochemistry , psychiatry , attention deficit hyperactivity disorder , gene
Objective: The aim of the study was to characterize the in vitro pharmacology of novel psychoactive substances (NPS) found in “ivory wave” including the methylphenidate‐like pipradrol derivatives desoxypipradrol (2‐diphenylmethylpiperidine, 2‐DPMP) and diphenylprolinol (diphenyl‐2‐pyrrolidinemethanol, D2PM) as well as the pyrovalerone cathinones 3,4‐methylenedioxypyrovalerone (MDPV) and naphyrone (bath salts). Methods: We assessed 3H‐monoamine uptake and reverse transport in HEK 293 cells expressing the human serotonin‐, norepinephrine‐, or dopamine reuptake transporters (SERT, NET, or DAT, respectively). Binding affinities at monoaminergic receptors were assessed using displacement of radioactive ligands. Results: D2PM and 2‐DPMP were selective catecholamine transporter inhibitors without transporter‐mediated substrate‐releasing properties similar to methylphenidate. 2‐DPMP was an equally potent DAT/NET inhibitor to methylphenidate, while D2PM was less potent. Compared with classical stimulants, 2‐DPMP was a 10‐fold more potent DAT blocker compared with cocaine. The pharmacological profile of the pipradrol‐drivatives was similar to that of the pyrovalerone cathinones MDPV and naphyrone. MDPV very potently inhibited NET and DAT but not SERT. Naphyrone was equipotent at all transporters. Both MDPV and naphyrone did not release monoamines. None of the compounds exhibited relevant affinity to monoaminergic receptors. Conclusion: Taken together the pipradrol derivatives and the pyrovalerone cathinones are potent and with the exception of naphyrone selective catecholamine uptake inhibitors in line with their potent and prolonged psychostimulant actions. The pharmacological profile is also likely associated with high abuse liability and an increased risk of psychiatric complications. Grant Funding Source : Swiss National Science Foundation