Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-25T04:40:14.830Z Has data issue: false hasContentIssue false
  • English
  • Français

Clozapine and D1/D2 Antagonism in Extrapyramidal Functions

Published online by Cambridge University Press:  06 August 2018

Jes Gerlach  and
Lars Hansen
Jes Gerlach*
Affiliation:
St Hans Hospital, Department P, DK-4000 Roskilde, Denmark
Lars Hansen
Affiliation:
St Hans Hospital, Department P, DK-4000 Roskilde, Denmark
*
Correspondence
Get access Rights & Permissions [Opens in a new window]

Abstract

One of the main advantages of clozapine is that it rarely produces extrapyramidal syndromes and tardive dyskinesia. This advantage is linked to the atypical biochemical profile of clozapine, especially its combined and low blockade of D1 and D2 receptors. The level of D2 receptor blockade is too low to induce extrapyramidal side-effects, and D1 antagonists have a lower extrapyramidal side-effect potential than traditional D2 neuroleptics, especially with respect to dystonia. The combined and balanced D1/D2 receptor blockade may prevent the development of a dysbalance between D1/D2 receptor function (in favour of D1) which otherwise might lead to tardive dyskinesia.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 160 , Issue S17: Clozapine - The Atypical Antipsychotic , May 1992 , pp. 34 - 37
Copyright
Copyright © The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andersson, U., Eckernäs, S.-A., Hartvig, P., et al (1990) Striatal binding of 11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding. Journal of Neural Transmission, 79, 215–226.CrossRefGoogle ScholarPubMed
Blin, J., Baron, J. C., Cambon, H., et al (1989) Striatal dopamine D2 receptors in tardive dyskinesia: PET study. Journal of Neurological and Neurosurgical Psychiatry, 52, 1248–1252.CrossRefGoogle ScholarPubMed
Carlsson, A. (1975) Receptor-mediated control of dopamine metabolism. In Pre- and Postsynaptic Receptors (eds E. Usdin & W. E. Bunney), pp. 49–63. New York: Dekker.Google Scholar
Casey, D. E. (1989) Clozapine: neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology, 99, S47–S53.CrossRefGoogle ScholarPubMed
Casey, D. E.(1991) Neuroleptic drug-induced extrapyramidal syndromes and tardive dyskinesia. Schizophrenia Research, 4, 109–120.CrossRefGoogle ScholarPubMed
Christensen, A. V. (1990) Long-term effects of dopamine D1 and D2 antagonists in vervet monkeys. Behavioural Neurology, 3, 49–60.Google Scholar
Coffin, V. L., Latranyi, M. B. & Chipkin, R. E. (1989) Acute extrapyramidal syndrome in Cebus monkeys: Development mediated by dopamine D2 but not D1 receptors. Journal of Pharmacology and Experimental Therapeutics, 249, 769–774.Google Scholar
Coffin, V. L., Barnett, A. & McHugh, D. T. (1991) Reversal of extrapyramidal side effects with SCH 39 166, a dopamine D1 receptor antagonist. Abstract from the ACNP 30th Annual Meeting, Puerto Rico, Dec. 9–13.Google Scholar
Collins, P., Broekkamp, C. L. E., Jenner, P., et al (1991) Drugs acting at D-1 and D-2 dopamine receptors induce identical purposeless chewing in rats which can be differentiated by cholinergic manipulation. Psychopharmacology, 103, 503–512.CrossRefGoogle ScholarPubMed
Fibiger, H. C. & Lloyd, K. G. (1984) Neurobiological substrates of tardive dyskinesia: the GABA hypothesis. Trends in Neuroscience, 7, 462–464.CrossRefGoogle Scholar
Fitton, A. & Heel, R. C. (1990) Clozapine. A review of its pharmacological properties and therapeutic use in schizophrenia. Drugs, 40, 722–747.CrossRefGoogle ScholarPubMed
Gerlach, J. (1979) Tardive dyskinesia. Danish Medical Bulletin, 26, 209–245.Google ScholarPubMed
Gerlach, J.(1985) Pathophysiological mechanisms underlying tardive dyskinesia. In Dyskinesia - Research and Treatment (eds D.E. Casey, T. N. Chase, A. V. Christensen, et al), pp. 98–103. Berlin: Springer-Verlag.CrossRefGoogle Scholar
Gerlach, J. & Casey, D. E. (1988) Tardive dyskinesia. Acta Psychiatrica Scandinavica, 77, 369–378.CrossRefGoogle ScholarPubMed
Gerlach, J. & Lublin, H. (1988) Tardive dyskinesia may be due to an increased D1/D2 receptor ratio in the brain. Schizophrenia Research, 1, 230.Google Scholar
Gerlach, J. & Simmelsgaard, H. (1978) Tardive dyskinesia during and following treatment with haloperidol, haloperidol + biperiden, thioridazine and clozapine. Psychopharmacology, 59, 105–112.CrossRefGoogle ScholarPubMed
Gerlach, J., Hansen, L. & Peacock, L. (1991) D1 dopamine hypothesis in tardive dyskinesia. In Biological Psychiatry. Proceedings from V World Congress in Biological Psychiatry (eds G. Racagni, N. Brunello & T. Fukuda), pp. 609–611. Amsterdam: Elsevier.Google Scholar
Gunne, L.-M. & Bárány, S. (1979) A monitoring test for the liability of neuroleptic drugs to induce tardive dyskinesia. Psychopharmacology, 63, 195–198.CrossRefGoogle ScholarPubMed
Gunne, L.-M., Häggström, J.-E. & Sjöquist, B. (1984) Association with persistent neuroleptic-induced dyskinesia of regional changes in brain GABA synthesis. Nature, 309, 347–349.CrossRefGoogle ScholarPubMed
Hansen, L. & Gerlach, J. (1991) Dopamine 1 and 2 receptor interaction in the development of dystonia and hypersensibility in Cebus monkeys. Biological Psychiatry, 29, 275S.Google Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozaril for the treatment-resistant schizophrenic. Archives of General Psychiatry, 45, 789–796.CrossRefGoogle ScholarPubMed
Klawans, H. L. (1973) The pharmacology of tardive dyskinesia. American Journal of Psychiatry, 130, 82–86.CrossRefGoogle Scholar
Klawans, H. L., Goetz, C. G. & Perlik, S. (1980) Tardive dyskinesia. Review and update. American Journal of Psychiatry, 137, 900–908.Google ScholarPubMed
Lieberman, J. A., Saltz, B. L., Johns, C. A., et al (1991) The effect of clozapine on tardive dyskinesia. British Journal of Psychiatry, 158, 503–510.CrossRefGoogle ScholarPubMed
Lublin, H. & Gerlach, J. (1988) Behavioural effects of dopamine D1 and D2 receptor agonists in monkeys previously treated with haloperidol. European Journal of Pharmacology, 153, 239–245.CrossRefGoogle ScholarPubMed
Marsden, C., Tarsy, D. & Baldessarini, R. (1975) Spontaneous and drug-induced movement disorders in psychotic patients. In Psychiatric Aspects of Neurological Disease (eds D. F. Benson & D. Blumer), pp. 219–265. New York: Grune & Stratton.Google Scholar
Meltzer, H. Y. (1989) Clinical studies of the mechanism of action of clozapine: the dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology, 99, S18–S27.CrossRefGoogle ScholarPubMed
Moore, D. C. & Bowers, M. B. Jr (1980) Identification of a subgroup of tardive dyskinesia patients by pharmacological probes. American Journal of Psychiatry, 173, 1202–1205.Google Scholar
Nordic Dyskinesia Group (1986) Effect of different neuroleptics in tardive dyskinesia and Parkinsonism. Psychopharmacology, 90, 423–429.Google Scholar
Parkenberg, H. & Pakkenberg, B. (1986) Clozapine in the treatment of tremor. Acta Neurologica Scandinavica, 73, 295–297.CrossRefGoogle Scholar
Peacock, L., Lublin, H. & Gerlach, J. (1990) The effects of dopamine D1 and D2 receptor agonists and antagonists in monkeys withdrawn from long-term neuroleptic treatment. European Journal of Pharmacology, 186, 49–59.CrossRefGoogle ScholarPubMed
Povlsen, U. J., Noring, U., Fog, R., et al (1985) Tolerability and therapeutic effect of clozapine. Acta Psychiatrica Scandinavica, 71, 176–185.CrossRefGoogle Scholar
Rosengarten, H., Schweitzer, J. W. & Friedhoff, A. J. (1983) Induction of oral dyskinesia in naive rats by D1 stimulation. Life Sciences, 33, 2479–2482.CrossRefGoogle ScholarPubMed
Seeman, P. (1980) Brain dopamine receptors. Pharmacology Review, 32, 229–313.Google ScholarPubMed
Simpson, G. W., Lee, J. H. & Shrivastava, R. K. (1978) Clozapine in tardive dyskinesia. Psychopharmacology, 56, 75–80.CrossRefGoogle ScholarPubMed
Van Tol, H. H. M., Bunzow, J. R., Guan, H. C., et al (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature, 350, 610–619.CrossRefGoogle ScholarPubMed
Waddington, J. L. (1989) Schizophrenia, affective psychoses, and other disorders treated with neuroleptic drugs: the enigma of tardive dyskinesia, its neurobiological determinants, and the conflict of paradigms. International Review of Neurobiology, 31, 297–353.CrossRefGoogle ScholarPubMed
Waddington, J. L., Cross, A. J., Gamble, S. J., et al (1983) Spontaneous orofacial dyskinesia and dopaminergic function in rats after 6 months of neuroleptic treatment. Science, 220, 530–534.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.