Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-28T03:39:30.406Z Has data issue: false hasContentIssue false

Olanzapine: preclinical pharmacology and recent findings

Published online by Cambridge University Press:  06 August 2018

Nick A. Moore*
Affiliation:
Lilly Research Centre Ltd, Erl Wood Manor, Windlesham, Surrey GU20 6PH

Abstract

Olanzapine possesses a broad pharmacological profile, interacting with a range of different neurotransmitter receptors. Although its affinity for muscarinic receptors is relatively greater than for dopamine receptors, on schedule-controlled behaviour olanzapine displays a profile resembling a dopamine antagonist. Likewise, in a test of cognitive function, olanzapine does not produce anticholinergic-like deficits. In drug discrimination assays, olanzapine substitutes for clozapine in clozapine-trained animals and clozapine generalises to olanzapine in olanzapine-trained animals. Olanzapine also reverses the behavioural deficits produced by inhibiting N-methyl-D-aspartate receptor glutamatergic transmission. This profile suggests that olanzapine will be effective against both positive and negative symptoms of schizophrenia while producing minimal extrapyramidal side-effects.

Type
Research Article
Copyright
Copyright © The Royal College of Psychiatrists, 1999 

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

Bakshi, V. P. & Geyer, M. A. (1995) Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic olanzapine. Psychopharmacology, 122, 198201.CrossRefGoogle ScholarPubMed
Bymaster, F. P., Calligaro, D. O., Falcone, J. F., et al (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology, 14, 8796.Google Scholar
Carey, G. J. & Bergman, J. (1997) Discriminative-stimulus effects of clozapine in squirrel monkeys: comparison with conventional and novel antipsychotic drugs. Psychopharmacology, 132, 261269.Google Scholar
Corbett, R., Camacho, F., Woods, A. T., et al (1995) Antipsychotic agents antagonize noncompetitive N-methyl-D-aspartate antagonist-induced behaviours. Psychopharmacology, 120, 6774.CrossRefGoogle Scholar
Gleason, S. D. & Shannon, H. E. D. (1997) Blockade of phencyclidine-induced hyperlocomotion by olanzapine, clozapine, and serotonin receptor subtype selective antagonists in mice. Psychopharmacology, 129, 7984.Google Scholar
Moore, N. A. (1996) Effect of olanzapine on responding maintained by a fixed interval/fixed ratio (FI/FR) schedule. Journal of Psychopharmacology, 10, A5.Google Scholar
Moore, N. A., Tye, N. C., Axton, M. S., et al (1992) The behavioral pharmacology of olanzapine, a novel atypical'antipsychotic agent. Journal of Pharmacology and Experimental Therapeutics, 262, 545551.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 (suppl. 10), 3744.Google Scholar
Porter, J. H. & Strong, S. E. (1997) Discriminative stimulus control with olanzapine: generalization to the atypical antipsychotic clozapine. Psychopharmacology, 128, 216219.Google Scholar
Varty, G. B. & Higgins, G. A. (1995) Reversal of dizocilpine-induced disruption of prepulse inhibition of an acoustic startle response by the 5HT2 receptor antagonist ketanserin. European Journal of Pharmacology, 287, 201205.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.