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Mouse Strain Sensitivity to Chlorpromazine and Amantadine Interaction

Implications for Management of Neuroleptic-Induced Dyskinesia and Tourette’s Syndrome

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Summary

Amantadine, a dopaminergic agonist, has been used in the management of neurolepticinduced dyskinesia and in Tourette’s syndrome. Genetic predisposition has been implicated in both of these movement disorders with a possible underlying abnormality in cerebral biogenic amine function. The effect of repeated administration of amantadine prior to chlorpromazine therapy on motor activity, whole brain dopamine, 5-hydroxytryptamine (5-HT, serotonin) and some major metabolites was studied as a function of mouse strain. Chlorpromazine-enhanced amantadine therapy produced increases in motor activity in outbred albino ICR mice but not in inbred BALB/c mice. Combined drug treatment prevented chlorpromazine-mediated reduction of brain dopamine, suggesting that amantadine antagonises this effect. Amantadine counteracted chlorpromazine-induced increases of BALB/c but not ICR mouse brain 5-hydroxyindoleacetic acid. This interaction may be useful in investigating the suggested imbalance between catecholamine and indoleamine systems implicated in drug-induced tremors and extrapyramidal disorders. The results suggest a genotypic-dependent amantadine-chlorpromazine interaction involving motor function and brain monoamines that may underlie individual susceptibility to the development of neuroleptic-induced dyskinesia and/or the variable responses to amantadine therapy in patients with tardive dyskinesia or Tourette’s syndrome.

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Correspondence to Prof. F. S. Messiha.

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Messiha, F.S. Mouse Strain Sensitivity to Chlorpromazine and Amantadine Interaction. Drug Invest 4, 89–94 (1992). https://doi.org/10.1007/BF03258386

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Keywords

  • Chlorpromazine
  • Amantadine
  • Drug Invest
  • Extrapyramidal Side Effect
  • Metanephrine