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.

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

“…METH is a psychostimulant used to treat several disorders, including attention deficit, narcolepsy and obesity (Cadet et al, 2007;Fleckenstein et al, 2007). Over use of this drug causes drug dependence and addiction and cause serious social problems.…”

“…The abuse of this highly addictive drug leads to the long-lasting changes in dopaminergic pathway of Central Nervous System (CNS). METH administration has been shown to produce long-term decreases in numerous measures of both dopaminergic and serotonergic function such as enzyme activity, monoamine content and monoamine transmitters in experimental animals as well as in human (Quinton and Yamamoto, 2006;Gold et al, 2009;Krasnova and Cadet, 2009;Guilarte et al, 2003;Kish, 2008;Kita et al, 2003;Cadet et al, 2007;Volz et al, 2007;Fleckenstein et al, 2007;Sofuoglu and Sewell, 2009). METH toxicity is frequently reported as a potential model of drug induced Parkinsonism, which is one of the most common movement disorders of the elderly.…”

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

“…Amphetamines and oxidative stress. Exposure to amphetamine or amphetamine derivatives has been shown to induce oxidative stress in the nervous system (Table 2), and this was the subject of previous reviews (Yamamoto and Bankson, 2005;Cadet et al, 2007). Methamphetamine and these drugs may be prevented by antioxidants.…”

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…Exposure to amphetamine or amphetamine derivatives has been shown to induce oxidative stress in the nervous system [305,306]. Methamphetamine and DͲamphetamine have been shown to increase ROS levels upon in vitro [307,308] or in vivo [309,310] exposure and the toxic effects of these drugs may be prevented by antioxidants.…”