clephedrone and monomethylpropion

Many cathinone analogs act as substrates or inhibitors at dopamine, norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine transporter substrates and inhibitors, such that potency at DAT > SERT is associated with high abuse potential, whereas potency at DAT < SERT is associated with low abuse potential. Quantitative structure-activity relationship (QSAR) studies with a series of 4-substituted methcathinone analogs identified volume of the 4-position substituent on the methcathinone phenyl ring as one structural determinant of both DAT vs. SERT selectivity and abuse-related behavioral effects in an intracranial self-stimulation procedure in rats. Subsequent modeling studies implicated specific amino acids in DAT and SERT that might interact with 4-substituent volume to determine effects produced by this series of cathinone analogs. These studies illustrate use of QSAR analysis to investigate pharmacology of cathinones and function of monoamine transporters.

Topics: Amphetamine; Animals; Behavior, Animal; Dopamine Plasma Membrane Transport Proteins; Fenfluramine; Humans; Methamphetamine; Methylamines; N-Methyl-3,4-methylenedioxyamphetamine; Norepinephrine Plasma Membrane Transport Proteins; Propiophenones; Psychotropic Drugs; Quantitative Structure-Activity Relationship; Rats; Self Administration; Serotonin Plasma Membrane Transport Proteins; Structure-Activity Relationship; Substance-Related Disorders