Doxepin: Effects on transport of biogenic amines in man

A new tricyclic antidepressant, doxepin, was evaluated for its ability to block the amine uptake mechanism of the peripheral adrenergic neuron and blood platelet in man. At low doses, there was no evidence of inhibition of the amine pump. However, at moderate doses (200–300 mg/day), necessary for effective antidepressant activity, doxepin was found to inhibit the pressor responses to tyramine and to reduce platelet 5-HT. These studies indicate that doxepin is a less potent inhibitor of the amine pump in the peripheral adrenergic neuron and blood platelet than is DMI or protriptyline. Doxepin, at the antidepressant dose level does alter biogenic amine uptake, an effect consistent with the biogenic amine hypothesis of depression. However, at 300 mg/day, a dose which blocks the pressor response to tyramine, antagonism of the antihypertensive effects of guanethidine and related drugs was demonstrated.This investigation was supported in part by Public Health Service Grant Numbers: MH 11468; 2 T01 HE 05545; 1 P11 GM 15431; 5 R01 HE 10842; 5 M01 RR 00095-10; RR 95.Dr. Oates is a Burroughs-Wellcome Scholar in Clinical Pharmacology.