EFFECT OF METOCLOPRAMIDE, ONDANSETRON AND GRANISETRON ON ALDOSTERONE SECRETION IN MAN

The plasma aldosterone response following the administration of drugs with antagonist and agonist activity at Serotonin 3 and 4 (5-HT3&4) re ceptors has been examined in 9 healthy male volunteers receiving the f ollowing four treatments i. v. in a randomised, cross-over sequence: o ndansetron 8 mg, granisetron 3 mg, metoclopramide 20 mg, and saline 20 ml. Metoclopramide significantly increased the mean plasma aldosteron e level to 196 % of basal level at 5 min. It rose to 234 % at 15 min a nd remained at more than 185 % of basal level for the duration of the experiment. The response to ondansetron and granisetron did not differ significantly from placebo. If dopamine antagonism is discounted, the results suggest that metoclopramide-induced aldosterone secretion res ults from its agonist activity at 5-HT4 receptors, although slow neuro nal depolarization via an unidentified receptor remains a possibility. Antagonism at the 5-HT3 receptor plays no role, as the selective anta gonist, granisetron, did not elicit a significant response. It seems u nlikely that the 5-HT4 receptor is the second, low affinity binding si te of ondansetron, unless it had no agonist activity at this receptor.