Hostname: page-component-77c89778f8-fv566 Total loading time: 0 Render date: 2024-07-21T12:10:36.284Z Has data issue: false hasContentIssue false
  • English
  • Français

Neuroleptic Treatment of Patients with Schizophrenia Mechanisms of Action and Clinical Significance

Published online by Cambridge University Press:  06 August 2018

Frits-axel Wiesel
Frits-axel Wiesel*
Affiliation:
Department of Psychiatry, Uppsala University, Ulleråker, S-750 17 Uppsala, Sweden
Get access Rights & Permissions [Opens in a new window]

Abstract

Neuroleptic drugs have been used in the treatment of schizophrenic patients for 40 years. In the 1960s it was proposed that the mechanism of action was a blockade of dopamine receptors; in vivo studies give strong evidence that a blockade of D2 dopamine receptors mediate the antipsychotic effect of classic neuroleptics. However, the antipsychotic effect of neuroleptics is synergistic with family treatment and social-skills training.

Type
II. The Treatment of Schizophrenia
Information
The British Journal of Psychiatry , Volume 164 , Issue S23: Integrated Approach to Schizophrenia , April 1994 , pp. 65 - 70
Copyright
Copyright © 1994 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

Alfredsson, G., Bjerkenstedt, L., Edman, G., et al (1984) Relationships between drug concentrations in serum and CSF, clinical effects and monoaminergic variables in schizophrenic patients treated with sulpiride or chlorpromazine. Acta Psychiatrica Scandinavica, 69 (suppl. 311), 49–74.CrossRefGoogle Scholar
Andén, N.-E., Roos, B.-E. & Werdinius, B. (1964) Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sciences, 3, 149–158.CrossRefGoogle Scholar
Andreasen, N. C. (1985) Positive vs. negative schizophrenia: a critical evaluation. Schizophrenia Bulletin, 11, 380–389.CrossRefGoogle ScholarPubMed
Angrist, B., Rotrosen, J. & Gershon, S. (1980) Responses to apomorphine, amphetamine, and neuroleptics in schizophrenic subjects. Psychopharmacology, 67, 31–38.CrossRefGoogle ScholarPubMed
Baldessarini, R., Cohen, B. M. & Teicher, M. H. (1988) Significance of neuroleptic dose and plasma level in the pharmacological treatment of psychoses. Archives of General Psychiatry, 45, 79–91.CrossRefGoogle ScholarPubMed
Blumberg, J. B., Taylor, R. E. & Sulser, F. (1975) Blockade by pimozide of a noradrenaline sensitive adenylate cyclase in the limbic forebrain: possible role of limbic noradrenergic mechanisms in the mode of action of antipsychotics. Journal of Pharmacy and Pharmacology, 27, 125–128.CrossRefGoogle ScholarPubMed
Bunney, B. S., Walters, J. R., Roth, R. H., et al (1973) Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity. Journal of Pharmacology and Experimental Therapeutics, 185, 560–571.Google ScholarPubMed
Carlsson, A. (1974) Antipsychotic drugs and catecholamine synapses. Journal of Psychiatric Research, 11, 57–64.CrossRefGoogle ScholarPubMed
Carlsson, A., Lindqvist, M., Magnusson, T., et al (1958) On the presence of 3-hydroxytyramine in brain. Science, 127, 471.CrossRefGoogle ScholarPubMed
Carlsson, A. & Lindqvist, M. (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxy-tyramine and normetanephrine in mouse brain. Acta Pharmacologica et Toxicologica, 20, 140–144.CrossRefGoogle ScholarPubMed
Carlsson, A. & Carlsson, A. (1990) Interactions between glutamatergic and monoaminergic systems within the basal ganglia – implications for schizophrenia and Parkinson's disease. Trends in Neuroscience, 13, 272–276.CrossRefGoogle ScholarPubMed
Clark, M. L., Ramsey, H. R., Rahhal, D. K., et al (1972) Chlorpromazine in chronic schizophrenia: the effect of age and hospitalization on behavioral dose–response relationships. Archives of General Psychiatry, 27, 479–483.CrossRefGoogle ScholarPubMed
Costall, B., Fortune, D. H., Naylor, R. J., et al (1975) Serotonergic involvement with neuroleptic catalepsy. Neuropharmacology, 14, 859–868.CrossRefGoogle ScholarPubMed
Creese, I., Burt, D. R. & Snyder, S. H. (1975) Dopamine receptor binding: differentiation of agonist and antagonist states with 3H-dopamine and 3H-haloperidol. Life Sciences, 17, 993–1002.CrossRefGoogle ScholarPubMed
Dahl, S. (1986) Plasma level monitoring of antipsychotic drugs. Clinical utility. Clinical Pharmacokinetics, 11, 36–61.CrossRefGoogle ScholarPubMed
Davis, J. M., Schaffer, C. B., Killian, G. A., et al (1980) Important issues in the drug treatment of schizophrenia. Schizophrenia Bulletin, 6, 70–87.CrossRefGoogle ScholarPubMed
Delay, J. & Deniker, O. (1957) Characteristiques psychophysiologiques des medicaments neuroleptiques. In The Psychotropic Drugs (eds Garattini, J. & Ghetti, V.), pp. 485–501. Amsterdam: Elsevier.Google Scholar
Falloon, J. R. H., Boyd, J. L., McGill, C. W., et al (1985) Family management in the prevention of morbidity of schizophrenia. Archives of General Psychiatry, 42, 887–896.CrossRefGoogle ScholarPubMed
Farde, L., Wiesel, F.-A., Halldin, C., et al (1988) Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Archives of General Psychiatry, 45, 71–76.CrossRefGoogle ScholarPubMed
Farde, L., Nordström, A.-L., Wiesel, F.-A., et al (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Archives of General Psychiatry, 49, 538–544.CrossRefGoogle ScholarPubMed
Gattaz, W. F., Kohlmeyer, K. & Gasser, G. (1990) Computer tomographic studies in schizophrenia. In Searches for the Cause of Schizophrenia (eds Häfner, H. & Gattaz, W. F.), pp. 242–256. Berlin: Springer.CrossRefGoogle Scholar
Gerlach, J. & Luhdorf, K. (1975) The effect of L-dopa on young patients with simple schizophrenia, treated with neuroleptic drugs: a double-blind cross-over trial with Madopar and placebo. Psychopharmacologia, 44, 105–110.CrossRefGoogle Scholar
Goldstein, M. J., Rodnick, E. H., Evans, J. R., et al (1978) Drug and family therapy in the aftercare of acute schizophrenics. Archives of General Psychiatry, 35, 1169–1177.CrossRefGoogle ScholarPubMed
Gottschalk, L. A. (1979) A preliminary approach to the problems of relating the pharmacokinetics of phenothiazines to clinical response with schizophrenic patients. In Pharmacokinetics of Psychoactive Drugs (ed. Gottschalk, L. A.), pp. 63–81. New York: Spectrum.Google Scholar
Härnryd, C., Bjerkenstedt, L., Björk, K., et al (1984a) Clinical evaluation of sulpiride in schizophrenic patients – a double-blind comparison with chlorpromazine. Acta Psychiatrica Scandinavica, 69 (suppl. 311), 7–30.CrossRefGoogle Scholar
Härnryd, C., Bjerkenstedt, L., Gullberg, B., et al (1984b) Time course for effects of sulpiride and chlorpromazine on monoamine metabolite and prolactin levels in cerebrospinal fluid from schizophrenic patients. Acta Psychiatrica Scandinavica, 69 (suppl. 3), 75–92.CrossRefGoogle Scholar
Hogarty, G. E., Goldberg, S. C. & Schooler, N. R. (1974) Drug and sociotherapy in the aftercare of schizophrenic patients. Archives of General Psychiatry, 31, 609–618.CrossRefGoogle ScholarPubMed
Hogarty, G. E., Andersson, C. M., Reiss, D. J., et al (1991) Family psycho-education, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. Archives of General Psychiatry, 48, 340–347.CrossRefGoogle Scholar
Johnstone, E. C., Crow, T. J., Frith, C. D., et al (1978) Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet, i, 848–851.CrossRefGoogle Scholar
Kane, J., Honigfeld, G., Singer, J., et al (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Archives of General Psychiatry, 45, 789–796.CrossRefGoogle ScholarPubMed
Karobath, M. & Leitich, H. (1974) Antipsychotic drugs and dopamine-stimulated adenylate cyclase prepared from corpus striatum of rat brain. Proceedings of the National Academy of Sciences, 71, 2915–2918.CrossRefGoogle ScholarPubMed
Kebabian, J. W., Petzold, G. L., Greengard, P. (1972) Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the ‘dopamine receptor”. Proceedings of the National Academy of Sciences, 69, 2145–2149.CrossRefGoogle Scholar
Kebabian, J. W. & Calne, D. B. (1979) Multiple receptors for dopamine. Nature, 277, 93–96.CrossRefGoogle ScholarPubMed
Keck, P. E., Cohen, B. M., Baldessarini, R. J., et al (1989) Time course of antipsychotic effects of neuroleptic drugs. American Journal of Psychiatry, 146, 1289–1292.Google ScholarPubMed
Leff, J., Kuipers, L., Berkowitz, R., et al (1985) A controlled trial of social intervention in the families of schizophrenic patients: two year follow-up. British Journal of Psychiatry, 146, 594–600.CrossRefGoogle ScholarPubMed
Lerner, Y., Lwow, E., Levitan, A., et al (1979) Acute high-dose parenteral haloperidol treatment of psychosis. American Journal of Psychiatry, 136, 1061–1064.Google ScholarPubMed
Longoni, R., Spina, L. & Dichiara, G. (1987) Permissive role of D-1 receptor stimulation for the expression of D-2 mediated behavioral responses: a quantitative phenomenological study in rats. Life Sciences, 41, 2135–2145.CrossRefGoogle ScholarPubMed
McEvoy, J. P., Hogarty, G. E. & Steingard, S. (1991) Optimal dose of neuroleptic in acute schizophrenia. Archives of General Psychiatry, 48, 739–745.CrossRefGoogle ScholarPubMed
Nordström, A.-L., Farde, L. & Halldin, C. (1992) Time course of D2-dopamine receptor occupancy examined by PET after single oral doses of haloperidol. Psychopharmacology, 106, 433–438.CrossRefGoogle ScholarPubMed
Nyback, H. & Sedvall, G. (1968) Effect of chlorpromazine on accumulation and disappearance of catecholamine formed from tyrosine 14C in brain. Journal of Pharmacology and Experimental Therapeutics, 162, 294–301.Google Scholar
Peroutka, S. J. & Snyder, S. H. (1980) Relationship of neuroleptic drug effects at brain dopamine, serotonin, alfa-adrenergic, and histamine receptors to clinical potency. American Journal of Psychiatry, 137, 1518–1522.Google Scholar
Praag, H. M. van (1977) The significance of dopamine for the mode of action of neuroleptics and the pathogenesis of schizophrenia. British Journal of Psychiatry, 130, 463–474.CrossRefGoogle ScholarPubMed
Putten, T. van Marder, S. R., May, P. R. A., et al (1985) Plasma levels of haloperidol and clinical response. Psychopharmacological Bulletin, 21, 69–72.Google ScholarPubMed
Roth, R. H., Murrin, L. C. & Walters, J. R. (1976) Central dopaminergic neurons: effects of alterations in impulse flow on the accumulation of dihydroxyphenylacetic acid. European Journal of Pharmacology, 36, 163–171.CrossRefGoogle ScholarPubMed
Sedvall, G., Alfredsson, G., Bjerkenstedt, L., et al (1975) Selective effects of psychoactive drugs on levels of monoamine metabolites and prolactin in cerebrospinal fluid of psychiatric patients. In Proceedings of the Sixth International Congress of Pharmacology in Proceedings of the Sixth International Congress of Pharmacology (ed. Airaksinen, H.), pp. 255–267. Forssa: Forssan Kirjapaino Oy.Google Scholar
Sedvall, G., Farde, L., Persson, A., et al (1986) Imaging of neurotransmitter receptors in the living human brain. Archives of General Psychiatry, 43, 995–1005.CrossRefGoogle ScholarPubMed
Seeman, P., Chau-Wong, M., Tedesco, J., et al (1975) Brain receptors for antipsychotic drugs and dopamine binding assay. Proceedings of the National Academy of Sciences, 72, 4376–4380.CrossRefGoogle Scholar
Sokoloff, P., Giros, B., Martres, M.-P., et al (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature, 347, 146–151.CrossRefGoogle ScholarPubMed
Sunahara, R. K., Guan, H.-C., O'Dowd, B. F., et al (1991) Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1 . Nature, 350, 614–619.CrossRefGoogle ScholarPubMed
Tol, H. H. M. van, 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, 610–614.Google ScholarPubMed
Tol, H. H. M. van, Wu, C. M., Guan, H.-C., et al (1992) Multiple dopamine D4 receptor variants in the human population. Nature, 358, 149–152.CrossRefGoogle ScholarPubMed
Wåhlinder, J., Skott, A., Carlsson, A., et al (1976) Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. Archives of General Psychiatry, 33, 501–505.CrossRefGoogle Scholar
Wiesel, F.-A. & Sedvall, G. (1975) Effect of antipsychotic drugs on homovanillic acid levels in striatum and olfactory tubercle of the rat. European Journal of Pharmacology, 30, 364–367.CrossRefGoogle ScholarPubMed
Wik, G. & Wiesel, F.-A. (1991) Regional brain glucose metabolism: correlations to biochemical measures and anxiety in patients with schizophrenia. Psychiatry Research: Neuroimaging, 40, 101–114.CrossRefGoogle ScholarPubMed
Wilson, J. C., Garbutt, J. C., Lanier, C. F., et al (1983) Is there a tardive dysmentia? Schizophrenia Bulletin, 9, 187–191.CrossRefGoogle Scholar
Wole-Helgodt, B., Borg, S., Fyrö, B., et al (1978) Clinical effects and drug concentrations in plasma and cerebrospinal fluid in psychotic patients treated with fixed doses of chlorpromazine. Acta Psychiatrica Scandinavica, 58, 149–173.CrossRefGoogle Scholar
Wolkin, A., Barouche, F., Wolf, A. P, et al (1989) Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. American Journal of Psychiatry, 146, 905–908.Google ScholarPubMed
Wyatt, R. C. (1991) Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin, 17, 325–351.CrossRefGoogle ScholarPubMed
Submit a response

eLetters

No eLetters have been published for this article.