The benzazepine SCH 23390 increases plasma levels of cortisol in the conscious dog.

The effect of neuroleptics on the hypothalamopituitary-adrenal system has been early recognized, but never adequately related to antipsychotic or side effects produced by dopamine antagonists. We are now presenting results showing that the newly characterized dopamine D-1 receptor antagonist, SCH 23390 (0.1 mg/kg i.v.) as well as the mainly dopamine D-2 receptor antagonists, haloperidol (0.1 mg/kg i.v.) and chlorpromazine (1 mg/kg i.v.), produced an increase of cortisol levels (108, 144 and 226% respectively, 20 min after the injection) determined by radioimmunoassay in blood samples collected from superficial veins of the legs of conscious dogs. The 5-HT2 receptor antagonist, cyproheptadine (0.2 mg/kg i.v.), did not modify the cortisol levels. These results suggest that cortisol increase is an effect common to neuroleptic compounds, independently of their relative antagonistic action at dopamine D-1 or D-2 receptors.