Effects of Enhancement and Antagonism of 5-Hydroxytryptamine Activity on the Influence of Metoclopramide on Gastric Emptying

This study examines the influence of the serotonergic system on the effect of metoclopramide on gastric emptying. Six subjects received the following pretreatments before metoclopramide and paracetamol: fluoxetine (5-HT uptake inhibitor); meterogoline (5-HT1 antagonist); pizotifen (5-HT2 antagonist) or methysergide (5-HT1 and 5-HT2 antagonist). One regimen consisted of metoclopramide (5-HT3 antagonist and 5-HT4 agonist) alone. Gastric emptying was measured by the mean cumulative fraction absorbed-time profiles of paracetamol. Methysergide/metoclopramide significantly delayed gastric emptying from 30 min onwards. Metoclopramide with either metergoline or pizotifen did not retard gastric emptying to the same extent, suggesting a greater influence with simultaneous 5-HT1 and 5HT2 blockade. Metoclopramide/fluoxetine caused a significant decrease in the fractional absorption of paracetamol at 5 min when compared to the metoclopramide regimen. It was assumed that the influence of metoclopramide was not optimal at this stage, therefore possibly indicating domination of 5-HT3 over 5-HT4 effects, resulting in gastric delay. It therefore seems as if all the 5-HT receptors present in the gut have a role to play in the control of gastric emptying.