D. Mckenna, S. Peroutka
Jan 1, 1990
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3
Influential Citations
191
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Journal
Journal of Neurochemistry
Abstract
3,4-Methylenedioxymethamphetamine (MDMA; also known as “Ecstasy”) is a ring-substituted phenylisopropylamine that is related to both amphetamines and hallucinogens, such as mescaline (Fig. 1). Although the drug was patented in 1914, interest in the compound was minimal until the past decade. During this period, MDMA began to be used as an adjunct to psychotherapy by certain therapists due to its purported ability to induce a state of reduced anxiety and lowered defensiveness (Downing, 1986; Greer and Tolbert, 1986). In addition, the recreational use of MDMA, particularly on college campuses, appears to have increased significantly in recent years (Peroutka, 1987). The human use of this agent is of concern due to the fact that MDMA and some of its congeners are selective serotonergic neurotoxins in laboratory animals. Partly as result of the recent interest in MDMA, numerous investigators have begun to explore the neurochemical effects of MDMA. During the past 3 years, over 80 publications on MDMA have appeared in the scientific literature. The following review attempts to provide a brief summary of recent data on the neurochemistry and neurotoxicity of MDMA and its derivatives. Administration of MDMA to animals elicits a characteristic biphasic response which, for convenience of discussion, can be categorized into acute and long-term effects. Some of the acute effects of MDMA appear to be related more directly to its behavioral and psychological effects, whereas the long-term effects have been correlated with the development of serotonergic neurotoxicity. It should be noted, however, that the acute and long-term effects cannot be considered in isolation from one another. Some of the effects, e.g., reduction in tryptophan hydroxylase (TPH) activity, manifest acutely, but may have long-term consequences; others, such as the rapid depletion of brain hydroxyindoles within hours following MDMA, appear to be unrelated to the slower, more persistent decreases in brain hydroxyindoles that are among the long-term neurochemical changes that are indicative of neurotoxicity. Table I summarizes the acute and long-term effects of MDMA.