Cerebral circulatory and metabolic effects of piribedil.
Two aspects of the cerebrovascular action of the putative dopaminergic agonist, piribedil, have been examined. The vasomotor responses of isolated feline middle cerebral artery to piribedil and its metabolite, S584, were first examined and the effects of piribedil upon cerebral blood flow, cerebral oxygen consumption and the electroencephalogram (EEG) were then investigated in anaesthetised baboons. Neither piribedil nor S584 displayed any marked vasomotor efficacy in vitro, with small changes in tension being observed only with large concentrations (greater than 10(-4) M). In the anaesthetised baboons, the administration of piribedil (0.1 and 1 mg/kg, i.v.) resulted in significant increases in cerebral blood flow (40 +/- 10% and 49 +/- 14%, respectively) (mean +/- S.E.M.) and cerebral oxygen consumption (13 +/- 10% and 17 +/- 6%) which were accompanied by an increase in low voltage fast activity of the EEG. Prior administration of the putative dopaminergic antagonist, pimozide (0.5 mg/kg), which itself was without significant effect upon cerebral blood flow and oxygen consumption, prevented the cerebral circulatory, metabolic and EEG alterations induced by piribedil (1 mg/kg). It would appear likely that the action of piribedil upon cerebral metabolic activity was principally responsible for the increases in cerebral tissue perfusion which followed its administration.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004569:Electroencephalography; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010215:Papio; D010868:Pimozide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010891:Piribedil / Q000494:pharmacology*
D010879:Piperazines; D010868:Pimozide; D010891:Piribedil