Amphetamines take two to tango: an oligomer-based counter-transport model of neurotransmitter transport explores the amphetamine action
Seidel S, Singer EA, Just H, Farhan H, Scholze P, Kudlacek O,
Holy M, Koppatz K, Krivanek P, Freissmuth M, Sitte HH.
Institute of Pharmacology,
Medical University Vienna,
Wahringer Str. 13a,
A-1090 Vienna, Austria.
Mol Pharmacol. 2005 Jan;67(1):140-51


Amphetamine congeners [e.g., 3,4-methylenedioxymetamphetamine (MDMA), or "ecstasy"] are substrates for monoamine transporters (i.e., the transporters for serotonin, norepinephrine, and dopamine); however, their in vivo-action relies on their ability to promote monoamine efflux. The mechanistic basis for this counter transport remains enigmatic. We tested the hypothesis that outward transport is contingent on the oligomeric nature of neurotransmitter transporters by creating a concatemer of the serotonin transporter and the amphetamine-resistant GABA transporter. In cells expressing the concatemer, amphetamine analogs promoted GABA efflux and blunted GABA influx. In contrast, the natural substrates serotonin and GABA only cause mutual inhibition of influx via the other transporter moiety in the concatemer. GABA efflux through the concatemer that was promoted by amphetamine analogs was blocked by the protein kinase C inhibitors GF109203X (bisindoylmaleimide I) and Go6983 (2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide). Thus, based on our observations, we propose that, in the presence of amphetamine analogs, monoamine transporters operate as counter-transporters; influx and efflux occur through separate but coupled moieties. Influx and efflux are coupled via changes in the ionic gradients, but these do not suffice to account for the action of amphetamines; the activity of a protein kinase C isoform provides a second stimulus that primes the inward facing conformation for outward transport.

Baboons like Ecstasy
Cocaine sensitisation
Anti-Parkinsonian effect
Cutaneous vasoconstriction
MDMA and the mitochondria
Ecstasy/MDMA and cannabis
Arginine-vasopressin release
Phosphatidylinositol turnover
MDMA, loud noise and the heart
MDMA, antihistamines and serotonin
MDMA, HIV and antiretroviral agents
Serotonin, noradrenline and dopamine
MDMA/polydrug users in the UK and Italy
Loud noise, nigrostriatal dopamine toxicity and MDMA
Urine testng by liquid chromatography-tandem mass spectrometry

and further reading

Future Opioids
BLTC Research
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