Similarity of clozapine and SCH 23390 in reserpinized rats suggests a common mechanism of action.
Clozapine at doses up to 100 mg/kg p.o. did not antagonize apomorphine-induced stereotypy in vehicle pre-treated rats. However, if the animals were injected with reserpine (30 mg/kg i.p.) 24 h prior to the test, then clozapine (3-100 mg/kg p.o.) produced a dose-related blockade of apomorphine-induced stereotypy. The blockade of apomorphine-induced stereotypy in reserpinized rats by clozapine was attenuated by the D-2 selective agonist LY 171555 but not the D-1 selective agonist SKF 38393. This profile of agonist reversal of antagonist blockade of apomorphine-induced stereotypy seen with clozapine was identical to that seen with the selective D-1 antagonist SCH 23390. Presumably, the D-2 agonist was active because D-1 receptor systems were inhibited (either at the receptor or at some other post-synaptic site) by clozapine or SCH 23390; this allowed a partial restoration of apomorphine-induced stereotypy via the D-2 system. Therefore, these data indicate that clozapine and SCH 23390 share a common mechanism of action via D-1 receptor systems.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D012110:Reserpine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D001552:Benzazepines; D003984:Dibenzazepines; D011954:Receptors, Dopamine; D012110:Reserpine; D003024:Clozapine; D001058:Apomorphine