Hostname: page-component-8448b6f56d-jr42d Total loading time: 0 Render date: 2024-04-24T19:00:53.843Z Has data issue: false hasContentIssue false
  • English
  • Français

Behavioural pharmacology of the new generation of antipsychotic agents

Published online by Cambridge University Press:  06 August 2018

N. A. Moore
N. A. Moore*
Affiliation:
Lilly Research Centre, Eli Lilly & Co., Erl Wood Manor, Windlesham, Surrey GU20 6PH. Tel: 44 (0) 1276 853553. Fax: 44 (0) 1276 853525. e-mail: Moore_NickA@Lilly.com
Get access Rights & Permissions [Opens in a new window]

Extract

Antipsychotic agents have been the mainstay in the management of schizophrenia for a number of years. Their therapeutic efficacy is primarily attributed to dopamine receptor antagonism (Creese et al, 1976), leading to a reduction in the positive symptoms of schizophrenia such as paranoia and hallucinations. Unfortunately, they have little effect on the negative symptoms (such as flattened affect, poverty of speech, anhedonia and social withdrawal) or cognitive deficits. The blockade of central dopamine receptors by classical antipsychotic agents also leads to the development of both acute and chronic motor disturbances (extrapyramidal side-effects) (EPS) (Meltzer, 1992).

Type
Research Article
Information
The British Journal of Psychiatry , Volume 174 , Issue S38: New antipsychotics - preclinical and clinical comparisons , May 1999 , pp. 5 - 11
Copyright
Copyright © 1999 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

Arnt, J. (1982) Pharmacological specificity of conditioned avoidance response inhibition in rats: Inhibition by neuroleptics and correlation to dopamine receptor blockade. Acta Pharmacologica et Toxicologica, 51, 321–329.Google Scholar
Arnt, J. (1995) Differential effects of classical and newer antipsychotics on the hypermotility induced by two dose levels of D-amphetamine. European Journal of Pharmacology, 283, 55–62.Google Scholar
Arnt, J. (1996) Inhibitory effects on the discriminative stimulus properties of D-amphetamine by classical and newer antipsychotics do not correlate with antipsychotic activity. Relation to effects on the reward system? Psychopharmacology, 124, 117–125.Google Scholar
Bakshi, V. P., Swerdlow, N. R. & Geyer, M. A. (1994) Clozapine antagonizes phencyclidine-induced deficits in sensorimotor gating of the startle response. Journal of Pharmacology and Experimental Therapeutics, 271, 787–794.Google ScholarPubMed
Bakshi, V. P. & Geyer, M. A. (1995) Antagonism of phencyclidine-induced deficits in prepulse inhibitio by the putative atypical antipsychotic olanzapine. Psychopharmacology, 122, 198–201.Google Scholar
Benvenga, M. J. & Leander, J. D. (1995) Olanzapine increases rates of punished responding in pigeons. Psychopharmacology, 119, 133–138.Google Scholar
Browne, R. G. & Koe, B. K. (1982) Clozapine and agents with similar behavioural and biochemical properties. In Drug Discrimination: Applications in CNS Pharmacology (eds Colpaert, F. C. & Slangen, J. F.), pp. 241–254. Amsterdam: Elsevier.Google Scholar
Bruhwyler, J., Cheide, E. & Mercier, M. (1990) Clozapine: An atypical neuroleptic. Neuroscience and Biobehavioural Reviews, 14, 357–363.Google Scholar
Bymaster, F. P., Calligara, D. O., Falcone, J. F., et al (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology, 14, 87–96.CrossRefGoogle ScholarPubMed
Carey, G. J. & Bergman, J. (1997) Discriminative-stimulus effects of clozapine in squirrel monkeys: Comparison with conventional and novel antipsychotic drugs. Psychopharmacology, 132, 261–269.Google Scholar
Casey, D. E. (1992) What makes a neuroleptic atypical. In Novel Antipsychotic Drugs (ed. Meltzer, H. Y.), pp. 241–251. New York: Raven Press.Google Scholar
Colpaert, F. C. & Slangen, J. F. (1982) Drug Discrimination: Applications in CNS Pharmacology. Amsterdam: Elsevier.Google Scholar
Cools, A. R., Prinssen, E. P. M. & Ellenbroek, B. A. (1995) The olfactory tubercle as a site of action of neuroleptics with an atypical profile in the paw test: Effect of risperidone, prothiphendyl, ORG-5222, sertindole, olanzapine. Psychopharmacology, 119, 428–439.CrossRefGoogle ScholarPubMed
Corbett, R., Hartman, H., Kerman, L. L., et al (1993) Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacology, Biochemistry & Behavior, 45, 9–17.CrossRefGoogle ScholarPubMed
Corbett, R., Camacho, F., Woods, A. T., et al (1995) Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviours. Psychopharmacology 120, 67–74.Google Scholar
Coward, D. M. (1992) General pharmacology of clozapine. British Journal of Psychiatry, 160 (suppl. 17), 5–11.Google Scholar
Coward, D. M. (1993) The pharmacology of clozapine-like atypical antipsychotics. In Antipsychotic Drugs and their Side-effects. Neuroscience Perspectives (ed. Barnes, T.), pp. 27–44. Oxford: Academic Press.Google Scholar
Coward, D. M., Imperato, A., Urwyler, S. & White, T. G. (1989) Biochemical and behavioural properties of clozapine. Psychopharmacology, 99, S6–S12.Google Scholar
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481–483.Google Scholar
Dunn, C. J. & Fitton, A. (1996) Sertindole. CNS Drugs, 5, 224–230.Google Scholar
Ellenbroek, B. A. (1993) Treatment of schizophrenia: A clinical and preclinical evaluation of neuroleptic drugs. Pharmacological & Therapeutics, 57, 1–78.CrossRefGoogle ScholarPubMed
Ellenbroek, B. A., Lubbers, L. J. & Cools, A. R. (1996) Activity of “Seroquel” (1C11204,636) in animal models for the atypical properties of antipsychotics: A comparison with clozapine. Neuropsychopharmacology, 15, 406–416.Google 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
Fulton, B. & Goa, K. L. (1997) Olanzapine: A review of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs, 53, 281–298.Google Scholar
Gleason, S. D. & Shannon, H. E. (1997) Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine and serotonin receptor subtype selective antagonists in mice. Psychopharmacology, 129, 79–84.Google Scholar
Goas, J. & Boston, J. E. (1978) Discriminative stimulus properties of clozapine and chlorpromazine. Pharmacology, Biochemistry & Behavior, 8, 235–241.Google Scholar
Goldstein, J. M. & Arvanitis, L. A. (1995) ICI 204,636 (Seroquel): A dibenzothiazepine atypical antipsychotic. Review of preclinical pharmacology and highlights of phase II clinical trials. CNS Drugs Reviews, I, 50–73.Google Scholar
Helmchen, H. (1989) Clinical experience with clozapine in Germany. Psychopharmacology, 99, S80–S83.Google Scholar
Hippius, H. (1989) The history of clozapine. Psychopharmacology, 99, S3–S5.Google Scholar
Hoenicke, E. M., Vanecek, S. A. & Woods, J. H. (1992) The discriminative stimulus effects of clozapine in pigeons: Involvement of 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors. Journal of Pharmacology and Experimental Therapeutics, 263, 276–284.Google Scholar
Janssen, P. A. J., Niemegeers, C. J. E., Awouters, F., et al (1988) Pharmacology of risperidone (R 64, 766), a new antipsychotic with serotonin-s2 and dopamine-D2 antagonsitic properties. Journal of Pharmacology and Expermental Therapeutics, 244, 685–693.Google Scholar
Kane, J. M., Honigfeld, G., Singer, J., et al (1989) Clozapine for the treatment-resistant schizophrenic: results of a US multicenter trial. Psychopharmacology, 99, S60–S63.Google Scholar
Kinon, B. J. & Lieberman, J. A. (1996) Mechanisms of action of atypical antipsychotic drugs: critical analysis. Psychopharmacology, 124, 2–34.Google Scholar
Leysen, J. E., Janssen, P. M. F., Megens, A. A., et al (1994) Risperidone: A novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. Journal of Clinical Psychiatry, 55 (suppl. 5), 5–12.Google Scholar
Maurel-Remy, S., Bervoets, K. & Millan, M. J. (1995a) Blockade of phencyclidine-induced hyperlocomotion by MDL 100,907 in rats reflects antagonism of 5HT2A receptors. European Journal of Pharmacology, 280, R9–R11.Google Scholar
Maurel-Remy, S., Audinot, V., Lejeune, F., et al (1995b) Blockade of phencyclidine-induced hyperlocomotion in rats by clozapine, MDL 100,907 and other antipsychotics with affinity at 5HT2a receptors. British Journal of Pharmacology, 114, 154P.Google Scholar
Meltzer, H. Y. (1992) The mechanism of action of clozapine in relation to its clinical advantages. In Novel Antipsychotic Drugs (ed. Meltzer, H. Y.), pp. 1–13 and preface. New York: Raven Press.Google Scholar
Meltzer, H. Y. (1994) An overview of the mechanism of action of clozapine. Journal of Clinical Psychiatry, 55, (SB) 47–52.Google Scholar
Migler, B. M., Warawa, E. J. & Malick, J. B. (1993) Seroquel: behavioural effects in conventional and novel tests for atypical antipsychotic drugs. Psychopharmacology, 112, 299–307.Google Scholar
Minchin, S. A. & Csernansky, J. G. (1996) Classification schemes for antipsychotic drugs. In Antipsychotics. Handbook of Experimental Pharmacology, Vol. 120 (ed. Csernansky, J. G.), pp. 1–42. Berlin: Springer.Google Scholar
Moore, N. A. & Axton, M. S. (1988) Production of climbing behaviour in mice requires both D1 and D2 receptor activation. Psychopharmacology, 94, 263–266.Google Scholar
Moore, N. A., Tye, N. C., Axton, M. S., et al (1992) The behavioural pharmacology of olanzapine a novel ‘atypical’ antipsychotic agent. Journal of Pharmacology and Experimental Therapeutics, 262, 545–551.Google Scholar
Moore, N. A., Calligaro, D. O., Wong, D. T., et al (1993) The pharmacology of Olanzapine and other new antipsychotic agents. Current Opinion in Investigation Drugs, 2(4), 281–293.Google Scholar
Moore, N. A., Rees, G. & Sanger, G. (1994a) Differential effects of olanzapine and other antipsychotic agents on stimulant-induced hyperactivity. Journal of Psychopharmacology, 8 (S1), A29.Google Scholar
Moore, N. A., Rees, G. & Sanger, G., et al (1994b) Effects of olanzapine and other antipsychotic agents on responding maintained by a conflict schedule. Behavioural Pharmacology, 5, 196–202.Google Scholar
Moore, N. A., Leander, J. D., Benvenga, M. J., et al (1997) Behavioral pharmacology of olanzapine: A novel antipsychotic drug. Journal of Clinical Psychiatry, 58 (S10), 37–44.Google ScholarPubMed
Nanry, K. P., Pollard, G. T. & Howard, J. L. (1995) Olanzapine moderately increases conflict responding but does not produce a benzodiazepine-like cue in rat. Drug Development Research, 34, 317–319.Google Scholar
Ogren, S. O. (1996) The behavioural pharmacology of typical and atypical antipsychotic drugs. In Antipsychotics: Handbook of Experimental Pharmacology, Vol. 120 (ed. Csernansky, J.G.), pp. 225–266. Berlin: Springer.Google Scholar
Ogren, S. O., Hall, H., Kohler, C., et al (1984) Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain. European Journal of Pharmacology, 102, 459–474.Google Scholar
Olney, J. W. & Farber, N. B. (1995) Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry, 52, 998–1024.Google Scholar
Porter, J. H. & Strong, S. E. (1997) Discriminative stimulus control with olanzapine: generalization to the atypical antipsychotic clozapine. Psychopharmacology, 128, 216–219.CrossRefGoogle Scholar
Sams-Dodd, F. (1997) Effect of novel antipsychotic drugs on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test. Behavioural Pharmacology, 8, 153–162.Google Scholar
Sanchez, C., Arnt, J., Dragsted, N., et al (1991) Neurochemical and in vivo pharmacological profile of sertindole, a limbic-selective neuroleptic compound. Drug Development Research, 22, 239–250.Google Scholar
Sanchez, C., Arnt, J., Costali, B., et al (1995) Sertindole: A limbic selective neuroleptic with potent anxiolytic effects. Drug Development Research, 34, 19–29.Google Scholar
Scheel-Kruger, J. (1992) Comparison of typical and atypical neuroleptics in the Morris swim maze. Behavioural Pharmacology, 3, 18.Google Scholar
Schotte, A., Janssen, P. F. M., Gommeren, W., et al (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology, 124, 57–73.Google Scholar
Seeger, T. F., Seymour, P. A., Schmidt, A. W., et al (1995) Ziprasidone (CP-88,059): A new antipsychotic with combined dopamine and serotonin receptor antagonist activity. Journal of Pharmacology & Experimental Therapeutics, 275, 101–113.Google Scholar
Skarsfeldt, T. (1996) Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics. Psychopharmacology, 124, 126–133.Google Scholar
Swerdlow, N. R., Zisook, D. & Taaid, N. (1994) Seroquel (1C11204,636) restores prepulse inhibition of acoustic startle in apomorphine-treated rats: Similarities to clozapine. Psychopharmacology, 114, 675–678.Google Scholar
Swerdlow, N. R., Braeff, D. L., Bakshi, V. P. & Geyer, M. A. (1996a) An animal model of sensorimotor gating deficits in schizophrenia predicts antipsychotic drug action. In Antipsychotics. Handbook of Experimental Pharmacology, Vo. 120 (ed. Csernansky, J.G.), pp. 289–312. Berlin: Springer.Google Scholar
Swerdlow, N. R., Bakshi, V. & Geyer, M. A. (1996b) ‘Seroquel’ (II 204,636) restores sensorimotor gating in phencyclidine-treated rats. Journal of Pharmacology and Experimental Therapeutics, 279, 1290–1299.Google Scholar
Varty, G. B. & Higgins, G. A. (1995a) Examination of drug-induced and isolation-induced disruptions of prepulse inhibition as models to screen antipsychotic drugs. Psychopharmacology, 122, 15–26.Google Scholar
Varty, G. B. & Higgins, G. A. (1995b) Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic startle response by the 5HT2 receptor antagonist ketanserin. European Journal of Pharmacology, 287, 201–205.Google Scholar
Wiley, J. L. & Porter, J. H. (1993) Serotonergic drugs do not substitute for clozapine in clozapine-trained rats in a two lever drug discrimination procedure. Pharmacology, Biochemistry & Behaviour, 43, 961–965.Google Scholar
Worms, P., Broekkamp, C. L. E. & Lloyd, K. (1983) Behavioural effects of neuroleptics. In Neuroleptics: Neurochemical, Behavioral, and Clinical Perspectives (eds Coyle, J. T. & Enna, S. J.), pp. 93–117. New York: Raven Press.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.