Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines

Methcathinone and methylone, the beta-ketone analogues of methamphetamine a nd 3,4-methylenedioxymethamphetamine (MDMA), respectively, were tested for neurotransmitter uptake inhibition in vitro. The beta-ketones were threefol d less potent than the nonketo drugs at inhibiting platelet serotonin accum ulation, with IC50's of 34.6 +/- 4.8 mu M and 5.8 +/- 0.7 mu M, respectivel y. Methcathinone and methylone were similar in potency to methamphetamine a nd 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 0.5 1 +/- 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 value s 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.