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1/4. Parkinsonism induced by indeloxazine hydrochloride in the elderly.

    Two elderly patients, aged 74 and 77 years, had typical symptoms of parkinsonism when treated with 60 mg of indeloxazine hydrochloride daily; the symptoms disappeared when indeloxazine was withdrawn. Results of animal studies indicate that indeloxazine increases slightly the dopamine content in the frontal cortex and striatum and markedly decreases levels of the dopamine metabolites 3,4-dihydroxy phenylacetic acid and homovanillic acid in most brain areas. In the two cases of parkinsonism, indeloxazine probably depressed dopamine release by inhibiting dopamine-containing nerve function, producing the parkinsonian symptoms. Since the brain dopamine content decreases in elderly persons, due care should be exercised when treating elderly patients with indeloxazine.
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2/4. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): one designer drug and serendipity.

    Through an unlikely series of coincidences and fortunate accidents, the development of Parkinson's disease in several illicit drug users was traced to their use of a meperidine analog contaminated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The discovery of a chemical capable of producing animal models of the disease has revitalized research efforts and resulted in important new information. The serendipitous finding also prompted consideration of what changes seem advisable if designer drugs are to be dealt with more efficaciously.
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3/4. Hemiparkinsonism. A human model for studying dopaminergic supersensitivity.

    The observation of a patient suffering from a parkinsonian syndrome, almost entirely expressed on the right side, and "on-off" attacks with rotatory movement of the trunk, led us to consider that the rotational model of animals may be reproduced in man. The symptoms presented by our patient may reflect a predominant degeneration in the nigrostriatal pathway of the left side. We suggest that his torsion behavior is due to hypersensitivity phenomenon of the dopaminergic receptors on this side.
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4/4. sertraline induced parkinsonism. A case report and an in-vivo study of the effect of sertraline on dopamine metabolism.

    We report a patient with a parkinsonian syndrome induced by sertraline (Zoloft), an SSRI antidepressant, whose symptoms resolved after the drug was discontinued. This case prompted us to investigate the effect of sertraline on dopamine metabolism in animals. sertraline (30 mg/kg, i.p.) or placebo (vehicle) was administered to two groups of six normal, anesthetized rats and using cerebral microdyalisis extracellular striatal levels of dopamine, the dopamine metabolites (HVA and DOPAC), as well as the serotonin metabolite 5-HIIA were monitored. In animals pre-treated with sertraline, DOPAC, HVA, and 5-HIAA levels were significantly decreased compared to control animals (p < 0.01). These data indicate that sertraline has an effect on dopamine metabolism, which may alter function in the striatum and induce a parkinsonian syndrome.
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