University of Toronto study finds amphetamines are converted in the brain into free radicals whose effects manifest and linger long after the amphetamine has left the body.
University of Toronto researchers have discovered a new mechanism for the neurodegenerative effects of amphetamines. These drugs are converted in the brain into free radicals, highly reactive molecules that cause neurodegenerative brain damage and whose effects manifest and linger long after the amphetamine has left the body.
"The question of whether amphetamines like ecstasy (MDMA) or methamphetamine (METH) cause neurodegeneration in humans is one of the most controversial areas in science today," says Professor Peter Wells of the Leslie Dan Faculty of Pharmacy, lead author of the study that appears in the April issue of the journal of the Federation of American Societies for Experimental Biology (FASEB Journal). "The short-term effects of these drugs -- hypothermia, electrolyte imbalances and an elevated risk of heart attack -- are well understood, but not their long-term consequences."
Wells and doctoral students Winnie Jeng, Annmarie Ramkissoon and Toufan Parman theorized that prostaglandin H synthase (PHS) -- an enzyme that synthesizes a range of hormones throughout mammalian life -- is the catalyst that transforms amphetamines into free radical products that react with oxygen in the body to enhance the formation of highly toxic reactive oxygen species. These toxic forms of oxygen are implicated in neurodegenerative diseases such as Alzheimer's and Parkinson's because of the increased oxidative stress they place on the body, resulting in irreversible damage to DNA, proteins and lipid membranes. Organs such as the brain, which lack abundant antioxidant protection, are particularly vulnerable to oxidative stress.