AbstractWe examined the possible involvement of 5‐HT4receptors in the gastroprokinetic effects of mosapride citrate (AS‐4370). In isolated longitudinal muscle myenteric plexus (LMMP) preparations from the guinea‐pig ileum, mosapride, cisapride, zacopride and metoclopramide enhanced electrically evoked contractions with EC50values of 74.2, 32.2, 50.3 and 1047.4 nM, respectively. The maximal increases in the amplitude of the contractions caused by mosapride, cisapride, zacopride and metoclopramide were 58, 78, 100 and 92% of those caused by 5‐HT, respectively. The enhancing effect of mosapride was non‐surmountably antagonised by high concentrations of tropisetron (10−‐7–3 ± 10−‐6M), but not by methysergide (10−‐6M) or ondansetron (10−‐6M). In the ileal LMMP preparations, mosapride, cisapride, zacopride and tropisetron had an inhibitory effect related to concentration on the 5‐HT (3 ± 10−‐7M) induced contractions with IC50values of 0.59, 0.71, 0.55 and 7.9 μM, respectively. Mosapride (10−‐8‐−10−‐5M) alone, unlike cisapride and zacopride, did not cause contraction in the ileal LMMP preparations. These results suggest that mosapride is a partial 5‐HT4receptor agonist and possesses 5‐HT4receptor antagonist activity at high concentrations. In conscious dogs with force transducers implanted, mosapride (I mg kg−1, i.v.) enhanced the antral motor activity in the postprandial state, and this enhancement was clearly antagonised by a high dose of tropisetron (10 mg kg−1h−1, i.v. infusion) that did not affect basal motor activity, indicating the involvement of 5‐HT4r