Hostname: page-component-745bb68f8f-grxwn Total loading time: 0 Render date: 2025-01-26T01:46:17.548Z Has data issue: false hasContentIssue false
  • English
  • Français

The pathophysiology of extrapyramidal side-effects of neuroleptic drugs

Published online by Cambridge University Press:  09 July 2009

C. D. Marsden  and
P. Jenner
C. D. Marsden*
Affiliation:
University Department of Neurology, Institute of Psychiatry, and King's College Hospital Medical School, London
P. Jenner
Affiliation:
University Department of Neurology, Institute of Psychiatry, and King's College Hospital Medical School, London
*
1Address for correspondence: Professor C. D. Marsden, University Department of Neurology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF.
Get access Rights & Permissions [Opens in a new window]

Synopsis

The mechanisms responsible for the production of major extrapyramidal side-effects (parkinsonism, akathisia, acute dystonic reactions, chronic tardive dyskinesias) are reviewed in the light of the complex effects of these drugs on cerebral dopamine systems.

Type
Research Article
Information
Psychological Medicine , Volume 10 , Issue 1 , February 1980 , pp. 55 - 72
Copyright
Copyright © Cambridge University Press 1980

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

Aghajanian, G. K. & Bunney, B. S. (1974). Pre- and post- synaptic feedback mechanisms in central dopaminergic neurons. In Frontiers of Neurology and Neuroscience Research (ed Seeman, P. and Brown, G. M.), pp. 4–11. University of Toronto Press: Toronto.Google Scholar
Aghajanian, G. K. & Bunney, B. S. (1977). Dopamine autoreceptors: pharmacological characterization by microiontophoretic single cell recording studies. Naunyn-Schmiedebergs Archiy für Pharmakologie 297, 1–8.CrossRefGoogle ScholarPubMed
Ahlenius, S. & Engel, J. (1971). Effects of small doses of haloperidol on turning behaviour. Journal of Pharmacy and Pharmacology 23, 301–302.CrossRefGoogle Scholar
Andén, N. E. (1972). Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and anti-acetylcholine drugs. Journal of Pharmacy and Pharmacology 24, 905–906.CrossRefGoogle ScholarPubMed
Andén, N. E., Carlsson, A. & Haggendal, J. (1969). Adrenergic mechanisms. Annual Reviews of Pharmacology 9, 119–134.CrossRefGoogle ScholarPubMed
Asper, H., Baggiolini, M., Burki, H. R., Lauener, H., Ruch, W. & Stille, G. (1973). Tolerance phenomena with neuroleptics: catalepsy, apomorphine stereotypies and striatal dopamine metabolism in the rat after single and repeated administration of loxapine and haloperidol. European Journal of Pharmacology 22, 287–294.CrossRefGoogle ScholarPubMed
Axelsson, J. & Thesleff, S. (1959). A study of supersensitivity in denervated mammalian skeletal muscle. Journal of Physiology (London) 147, 178–193.CrossRefGoogle ScholarPubMed
Ayd, F. J. (1961). A survey of drug-induced extrapyramidal reactions. Journal of the American Medical Association 175, 1054–1060.CrossRefGoogle ScholarPubMed
Barbeau, A. (1962). The pathogenesis of Parkinson's disease. A new hypothesis. Canadian Medical Association Journal 87, 802–807.Google ScholarPubMed
Bedard, P., Delean, J., Lafleur, J. & Larochelle, L. (1977). Haloperidol-induced dyskinesias in the monkey. Le Journal Canadien des Sciences Neurologique 4, 197–201.Google ScholarPubMed
Berger, B., Tassin, J. P., Blanc, B., Moyne, M. A. & Thierry, A. M. (1974). Histochemical confirmation for dopaminergic innervation of the rat cerebral cortex after destruction of the noradrenergic ascending pathways. Brain Research 81, 332–337.CrossRefGoogle ScholarPubMed
Bernheimer, H., Birkmayer, W., Hornykiewicz, O., Jellinger, K. & Seitelberg, F. (1973). Brain dopamine and the syndromes of Parkinson and Huntington: clinical, morphological and neurochemical correlations. Journal of Neurological Sciences 20, 415–455.CrossRefGoogle ScholarPubMed
Bertler, A. (1961). Effect of reserpine on the storage of catecholamines in brain and other tissues. Acta physiologica scandinavica 51, 75–83.CrossRefGoogle Scholar
Birkmayer, W. & Hornykiewicz, O. (1961). Der L-Dioxy-phenylalanin (= dopa) - Effekt bei der Parkinson-Akinese. Wiener klinische Wochenschrift 73, 787–788.Google Scholar
Bobon, D. P., Janssen, P. A. J. & Bobon, J. (eds.) (1970). Modern Problems in Pharmacopsychiatry. Volume 5: The Neuroleptics. S. Karger: Basel.Google Scholar
Bunney, B. S. & Aghajanian, G. K. (1976). d-Amphetamine induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Science 192, 391–393.CrossRefGoogle ScholarPubMed
Bunney, B. S., Walters, J. R., Roth, R. H. & Aghajanian, G. K. (1973). Dopaminergic neurons: effects of anti-psychotic drugs and amphetamines on single cell activity. Journal of Pharmacology and Experimental Therapeutlcs 185, 560–571.Google Scholar
Burt, D. R., Creese, I. & Snyder, S. H. (1976). Properties of 3H-haloperidol and 3H-dopamine binding associated with dopamine receptors in calf brain membranes. Molecular Pharmacology 12, 800–812.Google Scholar
Burt, D. R., Creese, I. & Snyder, S. H. (1977). Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196, 326–328.CrossRefGoogle ScholarPubMed
Calne, D. B., Teychenne, P. F., Claveria, L. E., Eastman, R., Greenacre, J. K. & Petrie, A. (1974). Bromocriptine in parkinsonism. British Medical Journal iv, 442–444.CrossRefGoogle Scholar
Carlsson, A. (1970). Biochemical implications of dopainduced actions on the central nervous system with particular reference to abnormal movements. In L-DOPA and Parkinsonism (ed. Barbeau, A. and McDowell, F. H.), pp. 205–213. Davis: Philadelphia.Google Scholar
Carlsson, A. (1977). Does dopamine play a role in schizophrenia? Psychological Medicine 7, 583–597.CrossRefGoogle ScholarPubMed
Carlsson, A. & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta pharmacologica et toxicologica 20, 140–144.CrossRefGoogle ScholarPubMed
Carlsson, A.Davis, J. N., Kehr, W., Lindqvist, M. & Atack, C. V. (1972 a). Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedebergs Archiv für Pharmakologie 275, 153–168.CrossRefGoogle ScholarPubMed
Carlsson, A., Kehr, W., Lindqvist, M., Magnusson, T. & Atack, C. V. (1972 b). Regulation of monoamine metabolism in the central nervous system. Pharmacological Reviews 24, 371–384.Google ScholarPubMed
Carroll, B. J., Curtis, G. C. & Kokmen, E. (1977). Paradoxical response to dopamine agonists in tardive dyskinesia. American Journal of Psychiatry 134, 785–789.Google ScholarPubMed
Carter, C. J. & Pycock, C. J. (1978). Studies on the role of catecholamines in the frontal cortex. British Journal of Pharmacology 42, 402P.Google Scholar
Chase, T. N. (1972). Drug-induced extrapyramidal disorders. Research Publications of the Association of Nervous and Mental Diseases 50, 448–471.Google ScholarPubMed
Christensen, A. V. (1973). Acute and delayed effects of a single dose of a neuroleptic drug. Acta physiologica scandinavica Suppl. 396, 78.Google Scholar
Christensen, A. V. & Møller-Nielsen, I. (1974). Influence of flupenthixol and flupenthixol-decanoate on methyiphenidate and apomorphine induced compulsive gnawing in mice. Psychopharmacologia (Berlin) 34, 119–126.CrossRefGoogle ScholarPubMed
Christensen, A. V., Fjalland, B. & Møller-Nielsen, I. (1976). On the supersensitivity of dopamine receptors induced by neuroleptics. Psychopharmacology 48, 1–6.CrossRefGoogle ScholarPubMed
Clement-Cormier, Y. C., Kebabian, J. W., Petzold, G. L. & Greengard, P. (1974). Dopamine-sensitive adenylate cyclase in mammalian brain: a possible site of action of antipsychotic drugs. Proceedings of the National Academy of Sciences (USA) 71, 1113–1117.CrossRefGoogle Scholar
Clow, A., Jenner, P. & Marsden, C. D. (1978). An experimental model of tardive dyskinesias. Life Sciences 23, 421–424.CrossRefGoogle ScholarPubMed
Clow, A., Jenner, P., Theodorou, A. & Marsden, C. D. (1979 a). Striatal dopamine receptors become supersensitive while rats are given trifluoperazine for six months. Nature 278, 59–61.CrossRefGoogle Scholar
Clow, A., Jenner, P. & Marsden, C. D. (1979 b). Changes in dopamine mediated behaviour during one year's neuroleptic administration. European Journal of Pharmacology 57, 365–375.CrossRefGoogle ScholarPubMed
Cools, A. R. & van Rossum, J. M. (1976). Excitation-mediating and inhibition-mediating dopamine receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. Psychopharmacologia (Berlin) 45, 243–254.CrossRefGoogle ScholarPubMed
Cools, A. R., Struyker, Boudier H. A. J. & van Rossum, J. M. (1976). Dopamine receptors: selective agonists and antagonists of functionally distinct types within the feline brain. European Journal of Pharmacology 37, 283–293.CrossRefGoogle ScholarPubMed
Corrodi, H., Fuxe, K. & Lidbrink, P. (1972). Interaction between cholinergic and catecholaminergic neurones in rat brain. Brain Research 43, 397–416.CrossRefGoogle ScholarPubMed
Costall, B. & Naylor, B. J. (1975). Neuroleptic antagonism of dyskinetic phenomena. European Journal of Pharmacology 33, 301–312.CrossRefGoogle ScholarPubMed
Cotzias, G. C., van Woert, M. H. & Schiffer, L. M. (1967). Aromatic amino acids and modification of parkinsonism. New England Journal of Medicine 276, 374.CrossRefGoogle ScholarPubMed
Crane, G. E. (1968). Tardive dyskinesia in patients treated with major neuroleptics: a review of the literature. American Journal of Psychiatry 124, 40–48.CrossRefGoogle ScholarPubMed
Crane, G. E. (1973). Persistent dyskinesia. British Journal of Psychiatry 122, 395–405.CrossRefGoogle ScholarPubMed
Davis, J. M. & Casper, R. (1977). Antipsychotic drugs: clinical pharmacology and therapeutic use. Drugs 14, 260–282.CrossRefGoogle ScholarPubMed
de Belleroche, J. & Bradford, H. F. (1978). Biochemical evidence for the presence of presynaptic receptors in dopaminergic nerve terminals. Brain Research 142, 53–68.CrossRefGoogle ScholarPubMed
Degkvitz, R. (1967). Über die Ursachen der persisteirenden extrapyramidalen Hyperkineser nach langfristiger. Anwendung von Neuroleptika Activitas Nervosa Superior (Praha) 12, 67–68.Google Scholar
Degkvitz, R. & Wenzel, W. (1967). Persistent extrapyramidal side effects after long-term application of neuroleptics.In Neuropsychopharmacology, International Congress Series No. 129 (ed. Brill, H.), pp. 608–615. Excerpta Medica: Amsterdam.Google Scholar
Delay, J. & Deniker, P. (1957). Caractéristiques neurophysiologiques des médicaments neuroleptiques. Rapport Symposium Internationale Médicaments Psychotropies, Milan 1957. In Psychotropic Drugs (ed. Garratini, S. and Ghetti, V.), pp. 485–501. Elsevier: Amsterdam.Google Scholar
Delay, J., Deniker, P. & Harl, J. M. (1952). Utilisation en thérapeutique psychiatrique d'une phenothiazine d'action centrale élective (4560 RP). Annales medico-psychologiques 110, 112–117.Google ScholarPubMed
Deneau, G. A. & Crane, G. E. (1968). Dyskinesia in rhesus monkeys tested with high doses of chlorpromazine. In Psychotropic Drugs and Dysfunctions of the Basal Ganglia (ed. Crane, G. E. and Gardner, J. R.). pp. 12–14. US Public Health Service Publications, no. 938: Washington, D.C.Google Scholar
Di Chiara, G., Porceddu, M. L., Vargiu, L., Argiolas, A. & Gessa, G. L. (1976). Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264, 564–567.CrossRefGoogle ScholarPubMed
Di Chiara, G., Porceddu, M. L., Fratta, W. & Gessa, G. L. (1977). Postsynaptic receptors are not essential for DA feedback regulation. Nature 267, 270–272.CrossRefGoogle ScholarPubMed
Di Chiara, G., Onali, P. L., Tissari, A. H., Porceddu, M. L., Morelli, M. & Gessa, G. L. (1978). Destruction of post-synaptic dopamine receptors prevents neuroleptic-induced activation of striatal tyrosine hydroxylase but not dopamine synthesis stimulation. Life Sciences 23, 691–696.CrossRefGoogle Scholar
Ehringer, H. & Hornykiewicz, O. (1960). Verteilung von Noradrenalin und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klinische Wochenschrift 38, 1236–1239.CrossRefGoogle Scholar
Eldridge, R. & Gottlieb, R. (1976). The primary hereditary dystonias: genetic classification of 768 families and revised estimate of gene frequency, autosomal recessive form and selected bibliography. In Advances in Neurology, volume 14 (ed. Eldridge, R. and Fahn, S.), pp. 457–474. Raven Press: New York.Google Scholar
Fann, W. E. & Lake, C. R. (1974). On the coexistence of parkinsonism and tardive dyskinesias. Diseases of the Nervous System 35, 324–326.Google Scholar
Farnebo, L.-O & Hamberger, B. (1971). Drug-induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta physiologica scandinavica suppl. 371, 35–44.CrossRefGoogle Scholar
Fleming, P., Makar, H. & Hunter, K. R. (1970). Levodopa in drug-induced extrapyramidal disorders. Lancet ii, 1186.CrossRefGoogle Scholar
Forrest, I. S. & Forrest, F. M. (1960). Urine color test for the detection of phenothiazine compounds. Clinical Chemistry 6, 11–15.CrossRefGoogle ScholarPubMed
Garcia-Munoz, M., Nicolaou, N., Tulloch, I. F., Wright, A. K. & Arbuthnott, G. W. (1977). Striato-nigral fibres – feedback loop or output pathway? Nature 265, 363–365.CrossRefGoogle ScholarPubMed
Garver, D. L., Davis, J. M., Dekirmenjian, H., Ericksen, S., Gosenfield, L. & Haraszti, J. (1976 a). Dystonic reactions following neuroleptics: time course and proposed mechanisms. Psychopharmacology 47, 199–201.CrossRefGoogle ScholarPubMed
Garver, D. L., Davis, J. M., Dekirmejian, H., Jones, F. D., Casper, B. & Haraszti, J. (1976b). Pharmacokinetics of red blood cell phenothiazine and clinical effects: acute dystonic reactions. Archives of General Psychiatry 33, 862–866.CrossRefGoogle ScholarPubMed
Geffen, L. B., Jessell, T. M., Cuello, A. C. & Iversen, L. L. (1976). Release of dopamine from dendrites in substantia nigra. Nature 260, 258–260.CrossRefGoogle ScholarPubMed
Gerlach, J. (1977a). Relationship between tardive dyskinesia, L-DOPA-induced hyperkinesia and parkinsonism. Psychopharmacology 51, 259–263.CrossRefGoogle ScholarPubMed
Gerlach, J. (1977b). The relationship between parkinsonism and tardive dyskinesia. American Journal of Psychiatry 134, 781–784.Google ScholarPubMed
Gerlach, J., Reisby, N. & Randrup, A. (1974). Dopaminergic hypersensitivity and cholinergic hypofunction in the pathophysiology of tardive dyskinesia. Psychopharmacologia (Berlin) 34, 21–35.CrossRefGoogle ScholarPubMed
Gey, K. F. & Pletscher, A. (1968). Acceleration of turnover of 14C-catecholamines in rat brain by chlorpromazine. Experientia 24, 335–336.CrossRefGoogle ScholarPubMed
Giorguieff, M. F., Le Floc'h, M. L., Westfall, T. C., Glowinski, J. & Beeson, M. J. (1976). Nicotonic effect of acetylcholine on she release of newly synthesised 3H- dopamine on rat striatal slices and cat caudate nucleus. Brain Research 106, 117–131.CrossRefGoogle Scholar
Giorguieff, M. F., Kemel, M. L. & Glowinski, J. (1977). Presynaptic effect of L-glutamic acid on dopamine release in rat striatal slices. Neuroscience Letters 6, 73–77.CrossRefGoogle ScholarPubMed
Glowinski, J., Iversen, L. L. & Axelrod, J. (1966). Storage and synthesis of norepinephrine in the reserpine-treated rat brain. Journal of Pharmacology and Experimental Therapeutics 151, 385–399.Google ScholarPubMed
Gnegy, M., Uzunov, P. & Costa, E. (1977). Participation of an endogenous Ca++-binding protein activator in the development of drug-induced super-sensitivity of striatal dopamine receptors. Journal of Pharmacology and Experimental Therapeutics 202, 558–564.Google Scholar
Grinspoon, L., Ewalt, J. R. & Shader, R. (1968), Psychotherapy and pharmacotherapy in chronic schizophrenia. American Journal of Psychiatry 124, 1645–1652.CrossRefGoogle ScholarPubMed
Groves, P.M., Wilson, C., Young, S. & Rebec, G. (1975). Self-inhibition by dopaminergic neurons. Science 190, 522–529.CrossRefGoogle ScholarPubMed
Gunne, L. M. & Barany, S. (1976). Haloperidol-induced tardive dyskinesia in monkeys. Psychopharmacology 50, 237–240.CrossRefGoogle ScholarPubMed
Handforth, A. & Sourkes, T. L. (1975). Inhibition by dopamine agonists of dopamine accumulation following λhydroxybutyrate treatment. European Journal of Pharmacology 34, 311–319.CrossRefGoogle ScholarPubMed
Heal, D. J., Green, A. R., Boullin, D. J. & Grahame-Smith, D. G. (1976). Single and repeated administration of neuroleptic drugs to rats: effect on striatal dopamine-sensitive adenylate cyclase and locomotor activity produced by tranylcypromine and L-tryptophan or L-dopa. Psychopharmacology 49, 287–300.CrossRefGoogle ScholarPubMed
Hirsch, S. R., Gaind, R., Rohde, P. D., Stevens, B. C. & Wing, J. K. (1973). Outpatient maintenance of chronic schizophrenic patients with long-acting fluphenazine: double blind placebo trial. Report to MRC Committee on Clinical Trials in Psychiatry. British Medical Journal i, 633–637.CrossRefGoogle Scholar
Hogarty, G. G., Goldberg, S. L. & Schooler, N. R. (1974). Drug and sociotherapy in the aftercare of schizophrenic patients. II. Two year relapse rates. Archives of General Psychiatry 31, 603–608.CrossRefGoogle ScholarPubMed
Hökfelt, T., Fuxe, K., Johansson, O. & Ljungdahl, A. (1974). Pharmacohistochemical evidence of the existence of dopamine nerve terminals in the limbic cortex. European Journal of Pharmacology 25, 108–112.CrossRefGoogle ScholarPubMed
Hornykiewicz, O. (1975). Parkinsonism induced by dopaminergic antagonists. In Advances in Neurology, volume 9 (ed. Calne, D. B., Chase, T. N. and Barbeau, A.), pp. 155–164. Raven Press: New York.Google Scholar
Hyttel, J. (1978). Dopamine-receptor binding and adenylate-cyclase activity in mouse striatal tissue in the supersensitivity phase after neuroleptic treatment. Psychopharmacology 59, 211–216.CrossRefGoogle ScholarPubMed
Iversen, L. L., Rogawski, M. A. & Miller, R. J. (1976). Comparison of the effects of neuroleptic drugs on preand postsynaptic dopaminergic mechanisms in the rat striatum. Molecular Pharmacology 12, 251–262.Google Scholar
Iversen, S. D. (1971). The effect of surgical lesions to frontal cortex and substantia nigra on amphetamine responses in rats. Brain Research 31, 295–311.CrossRefGoogle ScholarPubMed
Janssen, P. A. J., Niemegeers, C. J. E. & Schellekens, K. H. L. (1965). Is it possible to predict the clinical effects of neuroleptic drugs (major tranquillizers) from animal data? 1. Neuroleptic activity spectra for rats. Arzneimittel Forschung 15, 104–112.Google Scholar
Jus, A., Pineau, R., Lachance, R., Pelchat, G., Jus, K., Pires, P. & Villeneuve, R. (1976 a). Epidemiology of tardive dyskinesia. Part I. Diseases of the Nervous System 37, 210–214.Google Scholar
Jus, A., Pineau, R., Lachance, R., Pelchat, G., Jus, K., Pires, P. & Villeneuve, R. (1976 b). Epidemiology of tardive dyskinesia. Part II. Diseases of the Nervous System 37, 257–261.Google ScholarPubMed
Kazamatsuri, H., Chien, C. P. & Cole, J. O. (1972 a). Treatment of tardive dyskinesia. I. Clinical efficacy of a dopamine-depleting agent, tetrabenazine. Archives of General Psychiatry 27, 95–99.CrossRefGoogle ScholarPubMed
Kazamatsuri, H., Chien, C. P. & Cole, J. O. (1972 b). Treatment of tardive dyskinesia. II. Short term efficacy of dopamine-blocking agents haloperidol and thiopropazate. Archives of General Psychiatry 27, 100–103.CrossRefGoogle ScholarPubMed
Kebabian, J. W. & Calne, D. B. (1979). Multiple receptors for dopamine. Nature 277, 93–96.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 (USA) 69, 2145–2149.CrossRefGoogle Scholar
Klawans, H. L. (1973 a). The pharmacology of extra-pyramidal movement disorders. In Monograph in Neural Science (ed. Cohen, M. M.). S. Karger: Basel.Google Scholar
Klawans, H. L. (1973 b). The pharmacology of tardive dyskinesias. American Journal of Psychiatry 130, 82–86.CrossRefGoogle ScholarPubMed
Klawans, H. L. & Rubovits, R. (1974). Effect of cholinergic and anticholinergic agents on tardive dyskinesias. Journal of Neurology, Neurosurgery and Psychiatry 27, 941–947.CrossRefGoogle Scholar
Langer, S. Z. & Trendelenburg, U. (1966). The onset of denervation supersensitivity. Journal of Pharmacology and Experimental Therapeutics 151, 73–86.Google ScholarPubMed
Langer, S. Z., Draskoczy, P. R. & Trendelenberg, U. (1967). Time course of the development of supersensitivity to various amines in the nictitating membranes of the pithed cat after denervation and decentralization. Journal of Pharmacology and Experimental Therapeutics 157, 255–273.Google ScholarPubMed
Laverty, R. & Sharman, D. F. (1965). Modification by drugs of the metabolism of 3, 4-dihydroxyphenylethylamine, nor-adrenaline and 5-hydroxytryptamine in the brain. British Journal of Pharmacology 24, 759–772.Google Scholar
Leff, J. P. & Wing, J. K. (1971). Trials of maintenance therapy in schizophrenia. British Medical Journal iii, 599–604.CrossRefGoogle Scholar
Lindvall, O., Bjorklund, A., Moore, R. Y. & Stenevi, U. (1974). Mesencephalic dopamine neurons projecting to the neocortex. Brain Research 81, 325–331.CrossRefGoogle Scholar
Loga, S., Curry, S. & Lader, M. (1975). Interactions of orphenadrine and phenobarbitone with chlorpromazine: plasma concentrations and effects in man. British Journal of Clinical Pharmacology 2, 197–208.CrossRefGoogle ScholarPubMed
Marsden, C. D., Tarsy, D. & Baldessarini, R. J. (1975). Spontaneous and drug induced movement disorders in psychotic patients. In Psychiatric Aspects of Neurologic Disease (ed. Benson, D. F. and Blumer, D.), pp. 219–266. Grune & Stratton: New York.Google Scholar
Martres, M. P., Costentin, J., Baudry, M., Marcais, H., Protais, P. & Schwartz, J. C. (1977). Long-term changes in the sensitivity of pre- and post-synaptic dopamine receptors in mouse striatum evidence by behavioural and biochemical studies. Brain Research 136, 319–337.CrossRefGoogle Scholar
Meldrum, B. S., Anlezark, G. M. & Marsden, C. D. (1977). Acute dystonia as an idiosyncratic response to neuroleptic drugs in baboons. Brain 100, 313–326.CrossRefGoogle ScholarPubMed
Meyer, H. H. (1956). Die Behandlung exogener Psychosen mit Phenothiazenderivaten. L'Encéphale 45, 524–527.Google Scholar
Møller-Nielsen, I. & Christensen, A. V. (1975). Long term effects of neuroleptic drugs. Journal de Pharmacologie (Paris) 6, 277–282.Google Scholar
Møller-Nielsen, I., Christensen, A. V. & Fjalland, B. (1976). Receptor blockade and receptor supersensitivity following neuroleptic treatment. In Antipsychotic Drugs: Pharmacodynamics and Pharmacokinetics (ed Sedvall, G., Uvnas, B. and Zotterman, B.), pp. 257–260. Pergamon Press: Oxford.Google Scholar
Mones, R. J. (1973). Experimental dyskinesias in normal rhesus monkey. In Advances in Neurology, volume 1 (ed. Barbeau, A., Chase, T. N. and Paulson, G. W.), pp. 665–670. Raven Press: New York.Google Scholar
Muller, P. & Seeman, P. (1977). Brain neurotransmitters after long term haloperidol: dopamine, acetylcholine, serotonin, α-noradrenergic and naloxone receptors. Life Sciences 21, 1751–1758.CrossRefGoogle ScholarPubMed
National Institute of Mental Health (1964). Phenothiazine treatment in acute schizophrenia: effectiveness. Archives of General Psychiatry 10, 246–261.CrossRefGoogle Scholar
Nieoullon, A., Cheramy, A. & Glowinski, J. (1977). Release of dopamine in vivo from cat substantia nigra. Nature 266, 375–377.CrossRefGoogle ScholarPubMed
Nybäck, H. & Sedvall, G. (1970). Further studies on the accumulation and disappearance of catecholamines formed from tyrosine-14C in the mouse brain. European Journal of Pharmacology 10, 193–205.CrossRefGoogle ScholarPubMed
O'Keefe, R., Sharman, D. F. & Vogt, M. (1970). Effect of drugs used in psychoses on cerebral dopamine metabolism. British Journal of Pharmacology 38, 287–304.CrossRefGoogle Scholar
Olianas, M. C., De Montis, G. M., Concu, A., Tagliamonte, A. & Di Chiara, G. (1978). Intranigral kainic acid: evidence for nigral non-dopaminergic neurons controlling posture and behaviour in a manner opposite to the dopaminergic one. European Journal of Pharmacology 49, 223–232.CrossRefGoogle Scholar
Paden, C., Wilson, C. J. & Groves, P. M. (1976). Amphetamine-induced release of dopamine from the substantia nigra in vitro. Life Sciences 19, 1499–1506.CrossRefGoogle ScholarPubMed
Parkes, J. D., Bedard, P. & Marsden, C. D. (1976). Chorea and torsion in parkinsonism. Lancet i, 155.CrossRefGoogle Scholar
Paulson, G. W. (1973). Dyskinesia in monkeys. In Advances in Neurology, volume I (ed. Barbeau, A., Chase, T. N. and Paulson, G. W.), pp. 647–650. Raven Press: New York.Google Scholar
Reisine, T. D., Nagy, J. I., Fibiger, H. C. & Yamamura, H. I. (1979). Localisation of dopamine receptors in rat brain. Brain Research 169, 209–214.CrossRefGoogle ScholarPubMed
Roth, R. H., Walters, J. R., Murrin, L. C., Morgenroth, V. H. III (1975). Dopamine neurons: role of impulse flow and presynaptic receptors in the regulation of tyrosine hydroxylase. In Pre- and Post-Synaptic Receptors (ed. Usdin, E. and Bunney, W. E. Jr), pp. 5–46. Marcel Dekker: New York.Google Scholar
Rotrosen, J., Friedman, E. & Gershon, S. (1975). Striatal adenylate cyclase activity following reserpine and chronic chiorpromazine administration in rats. Life Sciences 17, 563–568.CrossRefGoogle ScholarPubMed
Sakalis, G., Curry, S. H., Mould, G. P. & Lader, M. H. (1972). Physiologic and clinical effects of chlorpromazine and their relationship to plasma level. Clinical Pharmacology and Therapeutics 13, 931–946.CrossRefGoogle ScholarPubMed
Salzman, N. P. & Brodie, B. B. (1956). Physiological disposition and fate of chlorpromazine and a method for its estimation in biological materials. Journal of Pharmacology and Experimental Therapeutics 118, 46–54.Google Scholar
Sassin, J. F. (1975). Drug-induced dyskinesias in monkeys. In Advances in Neurology, volume 10 (ed. Meldrum, B. S. and Marsden, C. D.), pp. 47–54. Raven Press: New York.Google Scholar
Scatton, B. (1977). Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration. European Journal of Pharmacology 46, 363–369.CrossRefGoogle ScholarPubMed
Schelkunov, E. L. (1967). Adrenergic effect of chronic administration of neuroleptics. Nature 214, 1210–1212.CrossRefGoogle ScholarPubMed
Seeber, U. & Kuchinsky, K. (1976). Dopamine-sensitive adenylate cyclase in homogenates of rat striata during ethanol and barbiturate withdrawal. Archives of Toxicology (Berlin) 35, 247–253.CrossRefGoogle ScholarPubMed
Seeman, P. & Lee, T. (1974). The dopamine-releasing actions of neuroleptics and ethanol. Journal of Pharmacology and Experimental Therapeutics 190, 131–140.Google ScholarPubMed
Seeman, P., Chau-Wong, M., Tedesco, J. & Wong, K. (1975). Brain receptors for antipsychotic drugs and dopamine: direct binding assay. Proceedings of the National Academy of Sciences (USA) 72, 4376–4380.CrossRefGoogle Scholar
Sigwald, J., Bouttier, D., Raymondeaud, C. & Piot, C. (1959). Quatre cas de dyskinesie catrice a evolution prolongée secondaire à un traitement par les neuroleptiques. Revue Neurologique 100, 751–755.Google Scholar
Simpson, G. M. (1970). Controlled studies of antiparkinsonism agents in the treatment of drug-induced extrapyramidal symptoms. Acta psychiatrica scandinavica. Suppl. 212, 44–51.CrossRefGoogle Scholar
Skirboll, L. R. & Bunney, B. S. (1979). Effects of chronic haloperidol treatment of spontaneous activity in the caudate nucleus. In Catecholamines: Basic and Clinical Frontiers (ed Usdin, E., Kopin, I. J. and Barchas, J.), pp. 634–636. Pergamon Press: New York.CrossRefGoogle Scholar
Smith, R. C. & Davis, J. M. (1976). Behavioural evidence for supersensitivity after chronic administration of haloperidol, clozapine and thioridazine. Life Sciences 19, 725–732.CrossRefGoogle ScholarPubMed
Smith, R. C., Tamminga, C. A., Haraszti, J., Paudey, G. W. & Davis, J. M. (1977). Effects of dopamine agonists in tardive dyskinesia. American Journal of Psychiatry 134, 763–768.Google ScholarPubMed
Spano, P. F., Trabucchi, M. & Di Chiara, G. (1977). Localisation of nigral dopamine sensitive adenylate cyclase on neurons originating from the corpus striatum. Science 196, 1343–1345.CrossRefGoogle ScholarPubMed
Steck, H. (1954). Le syndrome extrapyramidal et diencéphalique au cours des traitements au Largactil et au Serpasil. Annales medico-psychologiques 112, 737–743.Google ScholarPubMed
Strombom, U. (1977). Antagonism by haloperidol of locomotor depression induced by small doses of apomorphine. Journal of Neural Transmission 40, 191–194.CrossRefGoogle ScholarPubMed
Tarsy, D. & Baldessarini, R. J. (1973). Pharmacologically-induced behavioural supersensitivity to apomorphine. Nature 245, 262–263.Google ScholarPubMed
Tarsy, D. & Baldessarini, R. J. (1974). Behavioural super-sensitivity to apomorphine following chronic treatment with drugs which interfere with the synaptic function of catecholamines. Neuropharmacology 13, 927–940.CrossRefGoogle Scholar
Tarsy, D. & Baldessarini, R. J. (1976). The tardive dyskinesia syndrome. In Clinical Neuropharmacology, volume I (ed. Klawans, H. L.), pp. 29–61. Raven Press: New York.Google Scholar
Tassin, J. P., Stinus, L., Simon, M., Blanc, G., Thierry, A. M., le Moral, M., Cardo, B. & Glowinski, J. (1978). Relationship between the locomotor hyperactivity induced by A10 lesions and the destruction of the fronto-cortical dopaminergic innervation in the rat. Brain Research 141, 267–281.CrossRefGoogle ScholarPubMed
Thierry, A. M., Blanc, G., Sobel, A., Stinus, L. & Glowinski, J. (1973). Dopamine terminals in the rat cortex. Science 182, 499–501.CrossRefGoogle ScholarPubMed
Tolosa, E. S. (1978). Modification of tardive dyskinesia and spasmodic torticollis by apomorphine. Archives of Neurology 35, 459–462.CrossRefGoogle Scholar
Trendelenburg, U. (1963 a). Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacological Reviews 15, 225–276.Google ScholarPubMed
Trendelenburg, U. (1963b). Time course of changes in sensitivity after denervation of the nictitating membrane of the spinal cat. Journal of Pharmacology 142, 335–342.Google ScholarPubMed
Uhrbrand, L. & Faurbye, A. (1960). Reversible and irreversible dyskinesia after treatment with perphenazine, chlorpromazine, reserpine and electroconvulsive therapy. Psychopharmacologia (Berlin) 1, 408–419.CrossRefGoogle Scholar
van Rossum, J. M. (1966). Significance of dopamine-receptor blockade for mechanism of action of neuroleptic drugs Archives internationales de pharmacodynamie et de thérapie 160, 492–494.Google ScholarPubMed
von Voigtlander, P. F., Losey, E. G. & Triezenberg, H. J. (1975). Increased sensitivity to dopaminergic agents after chronic neuroleptic treatment. Journal of Pharmacology and Experimental Therapeutics 193, 88–94.Google Scholar
Weiss, B., Santelli, S. & Lusink, G. (1977). Movement disorders induced in monkeys by chronic haloperidol treatment. Psychopharmacology 53, 289–293.CrossRefGoogle ScholarPubMed
Yaryura-Tobias, J. A., Wolpert, A., Dana, L. & Merlis, J. (1970). Action of L-DOPA in drug-induced extrapyramidalism. Diseases of the Nervous System 31, 60–63.Google ScholarPubMed
Yeh, B. K., McNay, J. L. & Goldberg, L. I. (1969). Attenuation of dopamine renal and mesenteric vasodilatation by haloperidol in evidence for a specific dopamine receptor. Journal of Pharmacology and Experimental Therapeutics 168, 303–309.Google ScholarPubMed
Zivkovic, B., Guidotri, A.Revuelta, A. & Costa, E. (1975). Effect of thioridazine, clozapine and other antipsychotics on the kinetic state of tyrosine hydroxylase and on the turnover rate of dopamine in striatum and nucleus accumbens. Journal of Pharmacology and Experimental Therapeutics 194, 37–46.Google ScholarPubMed