Effects of amphetamines on mitochondrial function: role of free radicals and oxidative stress.
Amphetamine-like psychostimulants are associated with long-term decreases in markers for monoaminergic neurons, suggesting neuronal loss and/or damage within the brain. This long-term "toxicity" results from formation of free radicals, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS), although the mechanism(s) of ROS and RNS formation are unclear. Mitochondria are a major source of ROS and mitochondrial dysfunction has been linked to some neurodegenerative disorders. Amphetamines also inhibit mitochondrial function, although the mechanism involved in the inhibition is uncertain. This review coordinates findings on the multiple pathways for ROS and RNS and describes a hypothesis involving mitochondrial inhibition in the initiation of amphetamine-induced cellular necrosis.
Brown
Jeffrey M
JM
Department of Pharmacology and Experimental Therapeutics, L-613, School of Medicine, Boston University, 715 Albany Street, Boston, MA 02118, USA.
Yamamoto
Bryan K
BK
D000662:Amphetamines / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D000662:Amphetamines; D000697:Central Nervous System Stimulants; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D009584:Nitrogen; D004298:Dopamine