Factors influencing the response of the cerebral circulation to phenylethylamine.
The cerebrovascular actions of phenylethylamine, an amine that has been implicated in the pathogenesis of migraine, were investigated in 16 anesthetized baboons. The influence of monoaminergic blocking agents and of a specific inhibitor of monoamine oxidase upon the cerebral circulatory and metabolic actions of phenylethylamine were examined. The reductions in cerebral blood flow (28 percent) and cerebral oxygen consumption (31 percent) that accompany the intracarotid administration of phenylethylamine (2 X 10(-6) moles per kilogram per minute) were unaffected by the prior administration of either phenoxybenzamine (1.5 mg per kilogram, IV) or pimozide (0.5 mg per kilogram, IV). The administration of phenoxybenzamine and pimozide per se did not significantly disturb cerebral blood flow or oxygen consumption. The ability of migraine patients to oxidatively deaminate phenylethylamine is reduced at the time of their attacks. In the present experiments, the administration of the monoamine oxidase type B inhibitor, deprenyl (1 mg per kilogram, IV), did not effect significant changes in cerebral blood flow or cerebral oxygen consumption. However, following deprenyl, the administration of phenylethylamine (4 X 10(-8) moles per kilogram per minute), a concentration which was without effect in normal animals, significantly reduced cerebral blood flow. Some of the possible mechanisms influencing the sensitivity of the cerebral circulation to phenylethylamine, and their relationship to migraine, are considered.
D000818:Animals; D001812:Blood-Brain Barrier; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000882:Haplorhini; D008881:Migraine Disorders / Q000139:chemically induced / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*; D012642:Selegiline / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D010643:Phenoxybenzamine; D010868:Pimozide; D012642:Selegiline; D009638:Norepinephrine