New insights into the mechanism of action of amphetamines.
Amphetamine is a psychostimulant commonly used to treat several disorders, including attention deficit, narcolepsy, and obesity. Plasmalemmal and vesicular monoamine transporters, such as the neuronal dopamine transporter and the vesicular monoamine transporter-2, are two of its principal targets. This review focuses on new insights, obtained from both in vivo and in vitro studies, into the molecular mechanisms whereby amphetamine, and the closely related compounds methamphetamine and methylenedioxymethamphetamine, cause monoamine, and particularly dopamine, release. These mechanisms include amphetamine-induced exchange diffusion, reverse transport, and channel-like transport phenomena as well as the weak base properties of amphetamine. Additionally, amphetamine analogs may affect monoamine transporters through phosphorylation, transporter trafficking, and the production of reactive oxygen and nitrogen species. All of these mechanisms have potential implications for both amphetamine- and methamphetamine-induced neurotoxicity, as well as dopaminergic neurodegenerative diseases.
Fleckenstein
Annette E
AE
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA. fleckenstein@hsc.utah.edu
Volz
Trent J
TJ
Riddle
Evan L
EL
Gibb
James W
JW
Hanson
Glen R
GR
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects; D006801:Humans; D008694:Methamphetamine / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D050493:Vesicular Monoamine Transport Proteins / Q000187:drug effects
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D008694:Methamphetamine