Multireceptor interactions of haloperidol on rat cerebral frontal cortex "in vitro"

As several side effects of neuroleptics would be related to their interactions with several neurotransmitter receptors (R) haloperidol action on muscarinic cholinergic (mACh) R on frontal cerebral cortex preparations was analyzed. Here we show that haloperidol was able to inhibit in a concentration dependent manner the binding of specific mAChR radiolabeled antagonist on cerebral cortex membranes. This effect would be related to its interaction on mAChR of the M1 subtype as haloperidol blocked the stimulation of phosphoinositides (PIs) turnover induced by low concentrations of carbachol similarly as the M1 antagonist pirenzepine. However at high carbachol concentrations haloperidol triggered a potentiating stimulation of PIs hydrolysis that was only blocked by the alpha 1 adrenergic antagonist prazosin indicating an alpha 1 agonistic action of haloperidol on these Rs. These multireceptor actions of haloperidol found "in vitro" would strengthen its association with "in vivo" neuroleptic-induced side effects.