Effect of metoclopramide and domperidone on aldosterone, 18-hydroxycorticosterone and prolactin secretion in the rhesus monkey

Abstract

This study was designed to investigate dopaminergic mechanisms in the control of corticosteroid secretion. Eight rhesus monkeys received metoclopramide (200 μg/kg) or domperidone (200 and 400 μg/kg) with 5% dextrose (vehicle), or with dopamine (4 μg/kg/min) infusions begun 60 min before administration of the dopamine antagonist. Metoclopramide, in the presence of vehicle, increased plasma aldosterone concentrations from 4.8 ± 0.6 ng/dl to a maximum of 36 ± 4.7 ng/dl and PRL concentrations from 7.6 ± 1.1 ng/ml to a maximum of 120.5 ± 8.0 ng/ml. Administration of metoclopramide resulted in a rise in plasma 18-hydroxycorticosterone from 10.2 ± 1.3 ng/dl to a maximum concentration of 49.6 ± 4.5 ng/dl. Plasma concentrations of electrolytes, PRA, plasma cortisol, 11-deoxycorticosterone, corticosterone, 18-hydroxy-11-deoxycorticosterone, were not altered by metoclopramide. Domperidone, in both doses, markedly increased plasma PRL concentrations but had no effect on plasma 18-OHB or aldosterone concentrations. Dopamine infusion inhibited the aldosterone response to metoclopramide and the prolactin response to metoclopramide and domperidone. The results of this investigation demonstrate that aldosterone responses to metoclopramide and prolactin responses to metoclopramide and domperidone, are mediated by their antagonist activity at dopamine receptors.