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Pharmacological characterization of designer cathinones in vitro
Author(s) -
Simmler LD,
Buser TA,
Donzelli M,
Schramm Y,
Dieu LH,
Huwyler J,
Chaboz S,
Hoener MC,
Liechti ME
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.02145.x
Subject(s) - mephedrone , pharmacology , chemistry , designer drug , cathinone , methamphetamine , monoamine neurotransmitter , mdma , amphetamine , receptor , drug , biochemistry , dopamine , medicine , serotonin
Background and Purpose Designer β‐keto amphetamines (e.g. cathinones, ‘bath salts’ and ‘research chemicals’) have become popular recreational drugs, but their pharmacology is poorly characterized. Experimental Approach We determined the potencies of cathinones to inhibit DA , NA and 5‐ HT transport into transporter‐transfected HEK 293 cells, DA and 5‐ HT efflux from monoamine‐preloaded cells, and monoamine receptor binding affinity. Key Results Mephedrone, methylone, ethylone, butylone and naphyrone acted as non‐selective monoamine uptake inhibitors, similar to cocaine. Mephedrone, methylone, ethylone and butylone also induced the release of 5‐ HT , similar to 3,4‐methylenedioxymethamphetamine ( MDMA , ecstasy) and other entactogens. Cathinone, methcathinone and flephedrone, similar to amphetamine and methamphetamine, acted as preferential DA and NA uptake inhibitors and induced the release of DA . Pyrovalerone and 3,4‐methylenedioxypyrovalerone ( MDPV ) were highly potent and selective DA and NA transporter inhibitors but unlike amphetamines did not evoke the release of monoamines. The non‐β‐keto amphetamines are trace amine‐associated receptor 1 ligands, whereas the cathinones are not. All the cathinones showed high blood–brain barrier permeability in an in vitro model; mephedrone and MDPV exhibited particularly high permeability. Conclusions and Implications Cathinones have considerable pharmacological differences that form the basis of their suggested classification into three groups. The predominant action of all cathinones on the DA transporter is probably associated with a considerable risk of addiction.