The goals of our research are to finish our investigations of the possible neurotoxic effects of 9 anorectic drugs currently marketed in the U.S. These drugs have pharmacologic and/or structural properties similar to the amphetamines which we have previously shown to be neurotoxin affecting serotonergic (5HT) and dopaminergic (DA) neurons. Thru use criteria must be met to consider a drug neurotoxic: long-term depletion of 5HT, DA or NE; loss of reuptake sites; and morphologic evidence of neurodegeneration. By comparing the neurotoxic dose of a drug to its potency as an anorectic, an estimate of its safety margin can be obtained. In addition to the neurochemical studies, selected drugs which show neurotoxicity will be investigated to determine the functional consequences of the neurochemical changes. Behavioral baselines will be established and sensitivity to disruption by various DA and 5HT agonists and antagonists will be determined before and after exposure to the neurotoxin. We would predict that tolerance would occur to drugs which act as agonists throgh the release of the affected monoamine and supersensitivity to antagonists of the affected monoamine. In addition to the anorectic drugs we propose to determine whether other amphetamine-related hallucinogens share the 5HT neurotoxic properties of MDA which we have recently demonstrated. A variety of amphetamine related hallucinogens will be investigated using the same sequence of neurochemical and behavioral testing as that which we have employed with the anorectic drugs. Finally, we intend to investigate the possible neurotoxic effects of chronically infused cocaine using the same procedures as for the anorectic drugs.
Showing the most recent 10 out of 26 publications
