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.