Society for Neuroscience
Abstracts, 24, 341.8 (1998)
Methcathinone
and 2-methylamino-1-(3,4-methylenedioxyphenyl)propan-1-one
(methylone) selectively inhibit plasma membrane catecholaminereuptake transporters.
Nicholas
V. Cozzi, Michael K. Sievert,
Alexander T. Shulgin,* Peyton Jacob III,** and Arnold E.
Ruoho
Department of Pharmacology, University of Wisconsin Medical
School, Madison, WI 53706
*1483 Shulgin Road, Lafayette, CA 94549
**Departments of Medicine and Psychiatry,
University of California San Francisco, San Francisco, CA 94110
Abstract
Methcathinone, the benzylic ketone analog of
methamphetamine (MA), and methylone, the benzylic ketone analog of
3,4-methylenedioxymethamphetamine (MDMA), were synthesized and tested for their
abilities to inhibit monoamine uptake in vitro. Methcathinone and methylone were threefold less potent than MA or MDMA at
inhibiting [3H]5-HT uptake into human
platelets, with IC50's of 31.4 ± 7.3 uM
and 5.8 ± 0.7 uM, respectively. In C6 glial cells stably expressing the rat dopamine transporter,
methcathinone and methylone were similar in potency
to MA and MDMA, with IC50's for [3H]DA uptake of 0.36 ±
0.06 uM and 0.82 ± 0.17 uM,
respectively. Methcathinone and methylone were also
similar in potency to MA and MDMA in C6 cells expressing the human norepinephrine transporter, with IC50's for [3H]NE accumulation of 0.51 ± 0.10 uM
and 1.2 ± 0.1 uM, respectively. The benzylic ketone moiety of
methcathinone and methylone had a large (tenfold) negative
impact on the abilities of these drugs to inhibit the vesicular monoamine
transporter (VMAT2) compared to MA and MDMA. In VMAT2-containing bovine chromaffin granules, the IC50's for [3H]5-HT
uptake were 103 ± 15 uM for methcathinone and 125 ±
16 uM for methylone. These
results indicate that methcathinone and methylone are
potent and selective inhibitors of plasma membrane catecholamine reuptake
transporters, with more modest effects at the serotonin reuptake transporter.
These drugs are essentially inactive at the vesicular monoamine transporter.
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