EFFECTS OF ENHANCEMENT AND ANTAGONISM OF 5-HYDROXYTRYPTAMINE ACTIVITYON THE INFLUENCE OF METOCLOPRAMIDE ON GASTRIC-EMPTYING

This study examines the influence of the serotonergic system on the ef fect of metoclopramide on gastric emptying. Six subjects received the following pretreatments before metoclopramide and paracetamol: fluoxet ine (5-HT uptake inhibitor); meterogoline (5-HT1 antagonist); pizotife n (5-HT2 antagonist) or methysergide (5-HT1 and 5-HT2 antagonist). One regimen consisted of metoclopramide (5-HT3 antagonist and 5-HT4 agoni st) alone. Gastric emptying was measured by the mean cumulative fracti on absorbed-time profiles of paracetamol. Methysergide/metoclopramide significantly delayed gastric emptying from 30 min onwards. Metoclopra mide with either metergoline or pizotifen did not retard gastric empty ing to the same extent, suggesting a greater influence with simultaneo us 5-HT1 and 5HT2 blockade. Metoclopramide/fluoxetine caused a signifi cant decrease in the fractional absorption of paracetamol at 5 min whe n compared to the metoclopramide regimen. It was assumed that the infl uence of metoclopramide was not optimal at this stage, therefore possi bly indicating domination of 5-HT3 over 5-HT4 effects, resulting in ga stric delay. It therefore seems as if all the 5-HT receptors present i n the gut have a role to play in the control of gastric emptying.