Dopamine autoreceptor and postsynaptic receptor blocking potency of neuroleptics.

Neuroleptic drugs have been shown to block brain dopamine (DA) receptors. The relative potency of neuroleptics at blocking DA postsynaptic receptors (PSRs) and autoreceptors (ARs) is less clear. To examine this question, the potency of 5 neuroleptics at inhibiting receptors (PSRs) and autoreceptors (ABs) is less clear. To examine this question, the potency of 5 neuroleptics at inhibiting the augmentation of mouse climbing behavior induced by a high dose of apomorphine (2.5 mg/kg) (presumably mediated by DA PSRs) was compared with their potency at inhibiting the suppression of climbing behavior induced by a low dose of apomorphine (0.45 mg/kg) (presumably mediated by DA Ars). Haloperidol and molindone had no AR-blocking ability even at doses that substantially blocked DA PSRs. Metoclopramide and fluphenazine had AR-blocking ability only at doses that produced substantial PSR blockade. Sulpiride blocked DA ARs at doses that had relatively litter PSR effect. It is concluded that neuroleptic drugs differ substantially in their relative potency at blocking DA ARs and PSRs.