Induction of functional down-regulation of
beta-adrenoceptors in rats by 2-phenylethylamine

Paetsch PR, Baker GB, Greenshaw AJ
Department of Psychiatry,
University of Alberta,
Edmonton, Canada.
J Pharm Sci 1993 Jan;82(1):22-4


The effects of chronic administration of antidepressant drugs and 2-phenylethylamine on beta-adrenoceptor function were assessed. Monoamine oxidase inhibitors [phenelzine sulfate, 5 or 10 mg kg-1 per day, and (-)-deprenyl HCl, 1 mg kg-1 per day] and 2-phenylethylamine HCl (10 mg kg-1 per day) were administered to male Sprague-Dawley rats via Alzet osmotic minipumps. On days 21 and 22, the motor-suppressant actions of the beta-adrenoceptor agonist salbutamol hemisulfate (3 mg kg-1 intraperitoneally after 15 min) were assessed as a measure of beta-adrenoceptor sensitivity. On day 28, the animals were killed, and their brains were used for the measurement of monoamine oxidase activity and concentrations of 2-phenylethylamine, an endogenous amine and a metabolite of phenelzine. Phenelzine sulfate at 10 mg kg-1 per day (but not 5 mg kg-1 per day) and the combination of (-)-deprenyl and 2-phenylethylamine resulted in a decrease in the response to salbutamol. These treatments also resulted in substantial increases in brain 2-phenylethylamine concentrations. The phenelzine treatments each resulted in an equivalent inhibition of brain monoamine oxidase activity. These results support the proposal that 2-phenylethylamine may, at least in part, mediate the effects of phenelzine on beta-adrenoceptor function.

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