Pharmacological characterization of designer cathinones in vitro.
OBJECTIVE
Designer β-keto amphetamines (e.g. cathinones, 'bath salts' and 'research chemicals') have become popular recreational drugs, but their pharmacology is poorly characterized.


METHODS
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.


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
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.
Division of Clinical Pharmacology and Toxicology, Departments of Biomedicine and Internal Medicine, University Hospital and University of Basel, Basel, Switzerland.
L D
LD
Simmler
T A
TA
Buser
M
M
Donzelli
Y
Y
Schramm
L-H
LH
Dieu
J
J
Huwyler
S
S
Chaboz
M C
MC
Hoener
M E
ME
Liechti
D000662:Amphetamines / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D015198:Designer Drugs / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D000662:Amphetamines; D015198:Designer Drugs; D013287:Illicit Drugs; D050480:Plasma Membrane Neurotransmitter Transport Proteins; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine