Biomimetic electrochemical synthesis of quinol-thioether conjugates:
their implication in the serotonergic neurotoxicity of amphetamine derivatives
Largeron M, Neudorffer A, Gramond JP, Fleury MB
Ann Pharm Fr 2003 May;61(3):164-72
ABSTRACTInjection of 3,4-methylenedioxyamphetamine (MDA) or 3,4-methylenedioxymethylamphetamine (MDMA or ecstasy) directly into the brain fails to reproduce the long-term effects observed after peripheral administration, implying an essential role for systemic metabolites in the development of toxicity. However, the precise identity of the metabolites participating in MDA and MDMA-mediated serotonergic neurotoxicity remains unclear: neither 3,4-alpha-methyldopamine, nor N-methyl-alpha-methyldopamine, major metabolites, produce neurotoxicity following peripheral administration. In vivo, these metabolites are oxidized to the corresponding orthoquinones, that readily react with protein and nonprotein sulphydryls including glutathione (GSH). The resulting quinol-thioether conjugates exhibit a variety of toxicological activities, which can be regulated by intramolecular cyclisation reactions that occur subsequent to oxidation. The ability of quinol-thioether conjugates to redox cycle and produce reactive oxygen species provides a rationale for the potential role of these metabolites in MDA and MDMA neurotoxicity. A biomimetic one-pot synthesis of 5-(GSH-S-yl)-N-Me-alpha-Me-DA involving addition of GSH to the electrogenerated orthoquinone species, is reported to evaluate its in vivo potential neurotoxicity.Club drugs
Deaths in New York
Long-term brain damage?
Toxic metabolites of MDMA?
MDMA and sympathetic activity
A distal axotomy of brain serotonin neurons?
A toxic intraneuronal metabolite of serotonin?
Electrophysiological evidence of 5-HT damage
Non-neurotoxic and neurotoxic serotonin-releasers
Ecstasy-induced toxicity and the dopamine transporter
MDMA (Ecstasy) : neuropharmacology and neurotoxicity
5-HT, 5-HIAA, norepinephrine, epinephrine and dopamine
Lack of serotonin neurotoxicity after intracerebral Ecstasy microinjection
and further reading
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World
The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family