The purpose of these studies is to determine the importance of free radical mechanisms in tardive dyskinesia (TD). Free radicals are cytotoxic substances containing one or more unpaired electrons. In recent years a number of different movement disorders have been proposed to be associated with free radical formation. Some of these disorders include Parkinson""""""""s disease, manganese-induced hyperkinesias, Hallervorden-Spatz disease, and MPTP-induced parkinsonism. In order to determine if free radicals are involved in the pathophysiology of TD, both human and animal experiments will be performed. In one set of experiments, the cerebrospinal fluid of patients on neuroleptics with and without TD will be measured for evidence of free radical activity. Additionally, alpha-tocopherol (vitamin E), a nontoxic free radical scavenger that crosses the blood-brain barrier, will be employed. The only known action of alpha-tocopherol is free radical scavenging. Patients with TD will be treated with a-tocopherol is free radical scavenging. Patients with TD will be treated with alpha-tocopherol to determine if such treatment reduces the severity of movement disorder. In the second set of experiments, alpha-tocopherol will be administered to rats treated long-term (up to one year) with the neuroleptic fluphenazine decanoate to determine if treatment with alpha-tocopherol reduces the incidence and severity of neurochemical (including measures of free radical activity) and neuropathological changes induced by neuroleptics. These experiments may furnish insight into the pathophysiological basis of TD and TD-like movement disorders, and may provide a viable treatment for some patients who develop the condition.
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