Olanzapine: preclinical pharmacology and recent findings.
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.
Moore
N A
NA
Lilly Research Centre Ltd, Windlesham, Surrey.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006801:Humans; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D000077152:Olanzapine; D014677:Pharmaceutical Vehicles; D010622:Phencyclidine / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012559:Schizophrenia / Q000188:drug therapy; D012601:Scopolamine / Q000494:pharmacology; D012934:Social Isolation
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D014677:Pharmaceutical Vehicles; D001569:Benzodiazepines; D010890:Pirenzepine; D012601:Scopolamine; D010622:Phencyclidine; D003024:Clozapine; D000077152:Olanzapine