title: Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms.
abstract: The amphetamines, including amphetamine (AMPH), methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA), are among abused drugs in the US and throughout the world. Their abuse is associated with severe neurologic and psychiatric adverse events including the development of psychotic states. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. The purpose of the present review is to summarize the toxic effects of AMPH, METH and MDMA. The paper also presents some of the factors that are thought to underlie this toxicity. These include oxidative stress, hyperthermia, excitotoxicity and various apoptotic pathways. Better understanding of the cellular and molecular mechanisms involved in their toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of amphetamine use disorders in humans.
authors: Molecular Neuropsychiatry Branch, DHHS/NIH/NIDA, Intramural Research Program, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA. jcadet@intra.nida.nih.gov
authors: Jean Lud
authors: JL
authors: Cadet
authors: Irina N
authors: IN
authors: Krasnova
authors: Subramaniam
authors: S
authors: Jayanthi
authors: Johnalyn
authors: J
authors: Lyles
mesh_terms: D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D005334:Fever / Q000139:chemically induced; D006801:Humans; D008694:Methamphetamine / Q000633:toxicity; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine