AbstractAlicyclic ester analogues of the gastroprokinetic benzamide metoclopramide (1) and its ester congener SDZ 205557 (2), a 5‐HT4receptor antagonist, were prepared byO‐alkylation of 4‐amino‐5‐chloro‐2‐methoxybenzoate withN‐(2‐chloroethyl) substituted alicyclic amines. The bromo and iodo analogue of compound13b(2‐(1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) were obtained by halogenation of dechloro‐13bwithN‐halogenated succinimides. The series was evaluated in functionalin vitroassays with regard to affinity for serotoninergic 5‐HT4, 5‐HT3and muscarinic M3receptors. The affinities for 5‐HT4and M3receptors were below 6.0 (pKBor pA2). On 5‐HT4receptors in guinea‐pig ileal longitudinal muscle and rat oesophagus, the majority of compounds revealed partial 5‐HT4receptor agonism susceptible to blockade by SDZ 205557, a reference 5‐HT4receptor antagonist (pKb= 7.25 − 7.73 (guinea‐pig ileum) and 7.09 — 7.43 (rat oesophagus)). The relative agonist potency was in the range of 5 – 303 % (5‐HT: 100 %). Compound13band its bromo analogue17were the most potent esters of the series. The enantiomers of13g((R)‐ and (S)‐2‐(2‐methyl‐1‐piperidinyl)ethyl 4‐amino‐5‐chloro‐2‐methoxybenzoate) interacted stereoselectively with 5‐HT4receptors and displayed enantiomeric potency ratios (R)/(S) of 4.3 — 8.7. There was an excellent correlation between (a) antagonist affinity on guinea‐pig ileum and rat oesophagus, (b) relative agonist potency on guinea‐pig ileum and rat oesophagus, and (c) between antagonist affinity and relative agonist potency within each assay (r2>0.91). The new compounds may serve as academic tools in evaluating the functional role of 5‐HT4receptors. The selective partial 5‐HT4receptor agonists presented in this paper may be useful to restore physiological motility and secretion in the gut with reduced or