A Biological Evaluation Of Some 2′-Substituted Analogs Of MPTP
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1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to produce a Parkinsonian syndrome in man (Davis et al., 1979; Langston et al., 1983) and to destroy the nigrostriatal dopaminergic pathway in monkeys (Burns et al., 1983; Langston et al., 1984a) and mice (Heikkila et al., 1984a; Hallman et al., 1985). The discovery that administration of such a simple chemical substance can reproduce the behavioral and pathological symptoms of Parkinson’s disease has led some investigators to suggest that idiopathic Parkinson’s disease may be caused by a compound present either in the environment or as an endogenous biological constituent (Snyder and D’Amato, 1986). Searches have been conducted for compounds structurally similar to MPTP which might be responsible for producing idiopathic Parkinson’s disease and thousands of compounds, either synthesized in the laboratory or isolated from natural sources, have been identified which share certain structural features with MPTP (Markey and Schmuff, 1986). Our laboratory has been involved in the synthesis and evaluation of the neurotoxic potential of numerous analogs of MPTP with the intent of defining the structural requirements for production of MPTP-like neurotoxicity so that we will be able to predict the likelihood that any particular compound will be an MPTP-like neurotoxin.
KeywordsDopaminergic Neuron Parkinsonian Syndrome Nigrostriatal Dopamine Neurotoxic Potential Dopaminergic Neurotoxicity
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