Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Mouse Strain Sensitivity to Chlorpromazine and Amantadine Interaction

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

  • 3 Accesses


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.

This is a preview of subscription content, log in to check access.


  1. Barbeau A, Powcher E. Genetics of early onset Parkinson’s disease. In Yahr (Ed.) Current concepts of Parkinson’s disease and related disorders, pp. 1–16, Excerpta Medica, Amsterdam, 1983

  2. Bachas JD, Ciaranello RD, Dominic JA, Deguchi T, Orenberg EK, et al. Genetic differences in mechanisms involving neuroregulators. Journal of Psychiatric Research 11: 347–360, 1974

  3. Borison RL, Davis JM. Amantadine in Tourette’s syndrome. Current Psychiatric Therapies 22: 127–130, 1983

  4. Borison RL, Ang L, Hamilton WJ, Diamond BI, Davis JM. Treatment approaches in Gilles de la Tourette syndrome. Brain Research Bulletin 11: 205–208, 1983

  5. Ciaranello RD, Hoffman H, Schire J, Axelrod J. Genetic regulation of the catecholamine biosynthetic enzymes II. Inheritance of tyrosine hydroxylase and phenyl-ethanolamine-N-methyltransferase. Journal of Biological Chemistry 250: 3204–3211, 1974

  6. Commings DG, Commings BG, Devor EJ, Cloninger CR. Detection of major gene for Gilles de la Tourette syndrome. American Journal of Human Genetics 36: 586–600, 1984

  7. Gianutsos G, Chute S, Dunn J. Pharmacological changes in dopaminergic systems induced by long-term administration of amantadine. European Journal of Pharmacology 110: 357–361, 1985

  8. Huntington G. On chorea. Medical Surgical Reports 26: 317–321, 1972

  9. Kalow W. The development of pharmacogenetics — a retrospective on the 75th birthday of Hans Herken. Klinische Wochenschrift 66: 229–235, 1988

  10. Keepers GA, Casey DE. Clinical management of acute neuroleptic-induced extrapyramidal disorders. Current Psychiatric Therapies 23: 139–157, 1986

  11. Klawans HL, Falk DK, Nausieda PA, Weiner WL. Gilles de la Tourette’s syndrome after long-term chlorpromazine therapy. Neurology 28: 1064–1066, 1978

  12. Knopp W, Fischer R, Beck J. Clinical implications of the relation between taste sensitivity and the appearance of extrapyramidal side effects. Diseases of the Nervous System 27: 729–735, 1966

  13. Maj J, Sowinska H, Baran L. Effects of amantadine, amphetamine and apomorphine on the locomotor activity in rats. Life Sciences 12: 511–518, 1973

  14. McQueen EG. Pharmacological basis of adverse drug reactions. In Avery (Ed.) Drug treatment: Principles and practice of clinical pharmacology and therapeutics, pp. 161–192, Adis Press, Sydney and New York, 1980

  15. Messiha FS. Mouse strain-dependent effect of amantadine on motility and brain biogenic amines. Archives Internationales de Pharmacodynamie et de Thérapie 302: 74–85, 1990

  16. Ng KY, Chase TN, Colburn RW. Dopa induced release of cerebral monoamines. Science 170: 76–77, 1970

  17. Pinder RM. Drug-induced tremor, pp. 445–461, Oxford University Press, New York, 1984

  18. Rao GP. Rett syndrome. Indian Journal of Pediatrics 24: 509–510, 1987

  19. Scatton B, Cheramy A, Besson M, Glowinski J. Increased synthesis and release of dopamine in the striatum of the rat after amantadine treatment. European Journal of Pharmacology 13: 131–133, 1970

  20. Stromberg V, Svensson TH, Waldeck B. On the mode of action of amantadine. Journal of Pharmaceutical Sciences 22: 959–962, 1970

  21. Thornburg JE, Moore K. A comparison of locomotor stimulant properties of amantadine and L- and d-amphetamine in mice. Neuropharmacology 11: 678–682, 1972

  22. Vesell ES. Pharmacogenetic perspectives gained from twin and family studies. Pharmacology and Therapeutics 41: 535–552, 1989

Download references

Author information

Correspondence to Prof. F. S. Messiha.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation


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