β-adrenoceptors and antidepressants: Possible 2-phenylethylamine mediation of chronic phenelzine effects

Effects of chronic administration of antidepressant drugs on β-adrenoceptor function were assessed. Tricyclics (imipramine 30 mg/kg/day, desipramine 5 and 10 mg/kg/day) and monoamine oxidase inhibitors [(±)-tranylcypromine 1 mg/kg/day, phenelzine 5 and 10 mg/kg/day] were administered to Male Sprague-Dawley rats ( n = 8), via Alzet 2ML2 osmotic minipumps for 28 days. Pumps were implanted subcutaneously in the interscapular region and replaced after 14 days. On days 21 and 22 motor-suppressant actions of the β-adrenoceptor agonist salbutamol (3 mg/kg intraperitoneally [IP]) were assessed as a measure of β-adrenergic receptor sensitivity. On day 28 the animals were killed and their brains used for measurement of drug levels and monoamine oxidase activity. Liver tissue was used to measure the trace amine 2-phenylethylamine. Each drug induced a decrease in the response to salbutamol. With phenelzine the decreased response to salbutamol was not observed at the lower dose. Differences in monoamine oxidase inhibition following phenelzine did not correspond to differential effects on functional β-adrenergic sensitivity. Levels of 2-phenylethylamine, an endogenous amine that is also a metabolite of phenelzine, were significantly higher in the 10-mg/kg/day phenelzine group. These data suggest that 2-phenylethylamine may be one mediator of the chronic actions of phenelzine on β-adrenoceptors.