Mechanisms of neurotransmitter release by amphetamines: a review.
Amphetamine and substituted amphetamines, including methamphetamine, methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs khat and ephedra, encompass the only widely administered class of drugs that predominantly release neurotransmitter, in this case principally catecholamines, by a non-exocytic mechanism. These drugs play important medicinal and social roles in many cultures, exert profound effects on mental function and behavior, and can produce neurodegeneration and addiction. Numerous questions remain regarding the unusual molecular mechanisms by which these compounds induce catecholamine release. We review current issues on the two apparent primary mechanisms--the redistribution of catecholamines from synaptic vesicles to the cytosol, and induction of reverse transport of transmitter through plasma membrane uptake carriers--and on additional drug effects that affect extracellular catecholamine levels, including uptake inhibition, effects on exocytosis, neurotransmitter synthesis, and metabolism.
Sulzer
David
D
Department of Psychiatry, Neurology and Pharmacology, New York State Psychiatric Institute, Columbia University, 650 W. 168th Street, Black Building Room 309, New York, NY 10032, USA. ds43@columbia.edu
Sonders
Mark S
MS
Poulsen
Nathan W
NW
Galli
Aurelio
A
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
D000662:Amphetamines; D002352:Carrier Proteins; D002395:Catecholamines; D000697:Central Nervous System Stimulants; D018377:Neurotransmitter Agents; D014179:Neurotransmitter Uptake Inhibitors