MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment
by
Verrico CD, Miller GM, Madras BK.
Department of Psychiatry, Division of Neurochemistry,
New England Primate Research Center,
Harvard Medical School,
1 Pine Hill Drive, Southborough,
MA, 01772-9102, USA.
Psychopharmacology (Berl). 2005 Oct 12;:1-15


ABSTRACT

RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA, designated as "Ecstasy" if illicitly marketed in tablet form) induces significant decrements in neuronal serotonin (5-HT) markers in humans, nonhuman primates, and rats as a function of dosing and dosing regimen. In rats, MDMA-mediated effects are attributed, in part, to selective high-affinity transport of MDMA into 5-HT neurons by the 5-HT transporter (SERT), followed by extensive 5-HT release. OBJECTIVES: To clarify whether SERT-selective effects of MDMA at human monoamine transporters can account for the reported MDMA-induced selective toxicity of serotonin neurons in primate brain. METHODS: We investigated the interaction of [(3)H](+/-, RS)- (+, S)- and (-, R)-MDMA with the human SERT, dopamine (DA) transporter (DAT), and norepinephrine (NE) transporter (NET) in stably transfected human embryo kidney (HEK)-293 cells. RESULTS: The human DAT, NET, and SERT actively transported [(3)H]RS(+/-)-MDMA saturably, stereoselectively, and in a temperature-, concentration-, and transporter-dependent manner. MDMA exhibited the highest affinity for the NET>>SERT>/=DAT, the same rank order for MDMA inhibition of [(3)H]DA, [(3)H]NE, and [(3)H]5-HT transport and stimulated release of the [(3)H]monoamines, which differed from reports derived from rodent monoamine transporters. The extent of MDMA-induced release of 5-HT was higher compared with release of DA or NE. CONCLUSIONS: The affinity of MDMA for the human SERT in transfected cells does not clarify the apparent selective toxicity of MDMA for serotonin neurons, although conceivably, its higher efficacy for stimulating 5-HT release may be a distinguishing factor. The findings highlight the need to investigate MDMA effects in DAT-, SERT-, and NET-expressing neurons in the primate brain and the therapeutic potential of NET or DAT inhibitors, in addition to SERT-selective inhibitors, for alleviating the pharmacological effects of MDMA.

MDMA
Methylone
'Club drugs'
Ecstasy slang
Protect and survive
'Generation Ecstasy'


Refs
and further reading

HOME
HedWeb
Nootropics
erythroxylum-coca.com
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Good Drug Guide

The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family