The effect of pizotifen, a serotonin antagonist, and of pirenzepine, a muscarinic antagonist, on hormonal responses to metoclopramide in healthy subjects.

To examine whether and how muscarinic or serotoninergic properties might contribute to the hormone stimulating action of the dopamine antagonist metoclopramide, the effect of oral single-dose pretreatment with pirenzepine (Gastrozepin) 50 mg, a muscarinic antagonist, pizotifen (Sandomigran) 1 mg, a serotonin antagonist, or placebo on the responses of prolactin, aldosterone, plasma renin activity (PRA), cortisol (hydrocortisone) and human growth hormone (HGH) to the i.v. injection of metoclopramide 10 mg was studied in 6 young healthy volunteers. For comparison, a mere placebo study was added. Whereas aldosterone response to metoclopramide and PRA remained unchanged, prolactin response was decreased by pizotifen from 43 +/- 6.5 to 24 +/- 9 ng/ml, p less than 0.05. Pizotifen decreased base-line cortisol from 10.5 +/- 0.5 to 6.6 +/- 0.6 microgram/dl and prevented the increase in cortisol after metoclopramide in responsive subjects. Both pizotifen and pirenzepine decreased HGH responsiveness to metoclopramide. It is concluded that cortisol and, partly, prolactin stimulation by metoclopramide are due to its serotoninergic properties and that HGH responsiveness to metoclopramide becomes explainable by both the serotoninergic and muscarinic potencies of the drug.

RCT Entities:   Population Interventions Outcomes