Inhibition of plasma membrane monoamine transporters by β-ketoamphetamines

Methcathinone and methylone, the beta-ketone analogues of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), respectively, were tested for neurotransmitter uptake inhibition in vitro. The beta-ketones were threefold less potent than the nonketo drugs at inhibiting platelet serotonin accumulation, with IC50's of 34.6 +/- 4.8 mu M and 5.8 +/- 0.7 mu M, respectively. Methcathinone and methylone were similar in potency to methamphetamine and MDMA at catecholamine transporters individually expressed in transfected glial cells. For dopamine uptake, IC50's were 0.36 +/- 0.06 mu M and 0.82 +/- 0.17 mu M, respectively; for noradrenaline uptake, IC50 values were 0.51 +/- 0.10 mu M and 1.2 +/- 0.1 mu M, respectively. In chromaffin granules, IC50's for serotonin accumulation were 112 +/- 8.0 mu M for methcathinone and 166 +/- 12 mu M for methylone, 10-fold higher than the respective values for methamphetamine and MDMA. Our results indicate that methcathinone and methylone potently inhibit plasma membrane catecholamine transporters but only weakly inhibit the vesicle transporter. (C) 1999 Elsevier Science B.V. All rights reserved.