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ICI 204, 636: A New Atypical Antipsychotic Drug

Published online by Cambridge University Press:  06 August 2018

Steven R. Hirsch ,
Christopher G. G. Link ,
Jeffrey M. Goldstein  and
Lisa A. Arvanitis
Steven R. Hirsch*
Affiliation:
Charing Cross and Westminster Medical School, London
Christopher G. G. Link
Affiliation:
Zeneca Pharmaceuticals, Mereside
Jeffrey M. Goldstein
Affiliation:
CNS Clinical Research, Zeneca Pharmaceuticals, Wilmington, Delaware, USA
Lisa A. Arvanitis
Affiliation:
CNS Clinical Research, Zeneca Pharmaceuticals, Wilmington, Delaware, USA
*
Professor Steven R. Hirsch, Department of Psychiatry, Charing Cross and Westminster Medical School, London W6 8RP
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Extract

The therapeutic effects of ‘classic’ (typical) antipsychotic agents lie in their ability to block central dopaminergic receptors – a property that is also responsible for the frequent occurrence of undesirable extrapyramidal side-effects (EPS). In contrast to these typical agents, clozapine alone has distinguished itself in humans – by virtue of its enhanced antipsychotic action and lack of concurrent EPS – as an atypical antipsychotic. However, the use of clozapine has been limited by the occurrence of agranulocytosis and, to a lesser extent, seizures (Alvir et al, 1993; Haring et al, 1994). The mechanism underpinning the atypical profile of clozapine remains elusive. One hypothesis suggests that it lies in clozapine's higher serotonin 5-HT2: D2 binding ratio, when compared with typical agents – a factor being considered as a predictor of atypicality (Meltzer, this issue; Meltzer et al, 1989). However, an emerging view is that it is not a single pharmacological action, but rather multiple properties that may define an atypical, clozapine-like compound (Lieberman, 1993).

Type
Research Article
Information
The British Journal of Psychiatry , Volume 168 , Issue S29: Current Issues in the Development of Atypical Antipsychotic Drugs , May 1996 , pp. 45 - 56
Copyright
Copyright © 1996 The Royal College of Psychiatrists 

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References

Alvir, J. J., Lieberman, J. A., Safferman, A. Z., et al (1993) Clozapine-induced agranulocytosis. Incidence and risk factors in the US. New England Journal of Medicine, 329, 162–167.CrossRefGoogle Scholar
Arvanitis, L. A., Miller, B. G. & Link, C. G. G. (1995) Seroquel™: an atypical antipsychotic agent. In Syllabus & Proceedings Summary of the 148th Annual Meeting of the American Psychiatric Association; May 23, 1995, abstract N32. Washington, DC: APA.Google Scholar
Bloom, F. E. & Kupfer, D. J. (1994) Psychopharmacology, The Fourth Generation of Progress. New York: Raven Press.Google Scholar
Borison, R. L., Arvanitis, L. A., Miller, B. G., et al (1995) Seroquel (ICI 204,636): a novel atypical antipsychotic (abstract N243). Presented at the 50th Annual Meeting of the Society of Biological Psychiatry; May 20, 1995. Biological Psychiatry, 37, 661.CrossRefGoogle Scholar
Borison, R. L., Arvanitis, L. A., Miller, B. G., et al (1996) Multicenter, placebo-controlled, double-blind safety and efficacy evaluation of ICI 204,636 in hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia. Journal of Clinical Psychopharmacology, 16, 158–169.CrossRefGoogle ScholarPubMed
Fabre, L. F., Arvanitis, L., Pultz, J., et al (1995) ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clinical Therapeutics, 17, 366–378.CrossRefGoogle ScholarPubMed
Goldstein, J. M. (1995a) Pre-clinical pharmacology of new atypical antipsychotics in late stage development. Expert Opinion on Investigational Drugs, 4, 291–298.CrossRefGoogle Scholar
Goldstein, J. M. (1995b) ICI 204,636 (Seroquel™): new preclinical research data confirm atypical antipsychotic actions. In New Research Program and Abstracts of the 148th Annual Meeting of the American Psychiatric Association; May 24, 1995 poster NR461. Washington, DC: APA.Google Scholar
Goldstein, J. M., Litwin, L. C., Sutton, E. B., et al (1993) Seroquel: electrophysiological profile of a potential atypical antipsychotic. Psychopharmacology, 112, 293–298.CrossRefGoogle ScholarPubMed
Goldstein, J. M. & Snyder, D. H. (1995) Effects of Seroquel™ and other atypical antipsychotics in primate models of EPS (abstract 193). Presented at the 50th Annual Meeting of the Society of Biological Psychiatry; May 19, 1995. Biological Psychiatry, 37, 646.CrossRefGoogle Scholar
Grace, A. A. & Bunney, B. S. (1995) Electrophysiological properties of midbrain dopamine neurons. In Psychopharmacology, the Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D. J.), pp. 162–177. New York: Raven Press.Google Scholar
Hamner, M. B., Arvanitis, L. A., Miller, B. G., et al (1995a) Lack of sustained elevation of plasma prolactin in schizophrenic patients treated with ICI 204,636 (Seroquel™). In New Research Program and Abstracts of the 148th Annual Meeting of the American Psychiatric Association; May 23, 1995 in New Research Program and Abstracts of the 148th Annual Meeting of the American Psychiatric Association; May 23, 1995, poster NR200. Washington, DC: APA.Google Scholar
Hamner, M. B., Arvanitis, L. A., Miller, B. G., et al (1995b) The effects of Seroquel (ICI 204,636) on plasma prolactin in patients with schizophrenia (abstract 322). Presented at the 50th Annual Meeting of the Society of Biological Psychiatry; May 20, 1995. Biological Psychiatry, 37, 683.CrossRefGoogle Scholar
Haring, C., Neudorfer, C., Schwitzer, J., et al (1994) EEG alterations in patients treated with clozapine in relation to plasma levels. Psychopharmacology, 114, 97–100.CrossRefGoogle ScholarPubMed
Hirsch, S. R. (1994) Seroquel: an example of an atypical antipsychotic drug (abstract). Neuropsychopharmacology, 10 (suppl. 1), 371S.Google Scholar
Hirsch, S. R., Arvanitis, L., Miller, B., et al (1994) A multicentre, double-blind, placebo-controlled comparison of low and high dosage regimens of Seroquel in the treatment of hospitalised patients with acute exacerbation of subchronic or chronic schizophrenia (abstract). European Neuropsychopharmacology, 4, 384–385.CrossRefGoogle Scholar
Huang, M. L., Van, P. A., Woestenborghs, R., et al (1993) Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy volunteers. Clinical Pharmacology and Therapeutics, 54, 257–268.CrossRefGoogle Scholar
Lieberman, J. A. (1993) Understanding the mechanism of action of atypical antipsychotic drugs. A review of compounds in development. British Journal of Psychiatry, 22 (suppl. 22), 7–18.CrossRefGoogle Scholar
Link, C., Arvanitis, L. A., Miller, B., et al (1994a) A multicentre, placebo-controlled, double-blind evaluation of Seroquel in hospitalised patients with acute exacerbation of chronic and subchronic schizophrenia (abstract). European Neuropsychopharmacology, 4, 385–386.CrossRefGoogle Scholar
Link, C., Smith, A., Miller, B., et al (1994b) A multicentre, double-blind, controlled comparison of Seroquel and chlorpromazine in the treatment of hospitalised patients with acute exacerbation of subchronic and chronic schizophrenia (abstract). European Neuropsychopharmacology, 4, 385.CrossRefGoogle Scholar
Meltzer, H. Y. (1995) Atypical antipsychotic drugs. In Psychopharmacology, the Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D. J.), pp. 1277–1286. New York: Raven Press.Google Scholar
Meltzer, H. Y., Matsubara, S. & Lee, J.-C. (1989) Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin-2 pKi values. Journal of Pharmacology and Experimental Therapeutics, 251, 238–246.Google Scholar
Meltzer, H. Y., Hirsch, S. R., Arvanitis, L. A., et al (1996) ICI 204,636, an atypical antipsychotic: an open-label, international, multicenter trial of efficacy and safety in patients with acute psychotic symptoms.Google Scholar
Migler, B. M., Warawa, E. J. & Malick, J. B. (1993) Seroquel: behavioral effects in conventional and novel tests for atypical antipsychotic drug. Psychopharmacology 112, 299–307.CrossRefGoogle ScholarPubMed
Saller, C. F. & Salama, A. I. (1993) Seroquel: biochemical profile of a potential atypical antipsychotic. Psychopharmacology, 112, 285–292.CrossRefGoogle ScholarPubMed
Simpsom, G. M. (1976) Neurological Rating Scale. In ECDEU Assessment Manual for Psychopharmacology (Revised 1976) (ed. Guy, W.). Rockville, Maryland: US Dept. Of Health, Education and Welfare, NIMH.Google Scholar
Simpsom, G. M. & Angus, J. W. S. (1970) A rating scale for extrapyramidal side effects. Acta Psychiatrica Scandinavica, 212 (suppl. 44), 11–19.CrossRefGoogle Scholar
Small, J. G., Hirsch, S. R., Arvanitis, L. A., et al (1996) The efficacy and safety of ICI 204,636 (Seroquel™) in patients with schizophrenia: high- and low-dose, double-blind comparison with placebo.Google Scholar
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