The enantiomers of the indolyl-2-oxoacetamide 5 were found to have 5-HT3 receptor partial agonist activity with (R)-5 having higher potency than (S)-5.In contrast to the plethora of 5-HT3 receptor antagonists that have been reported, 1,2 relatively few 5-HT 3 receptor agonists have been described. In addition to the natural agonist 5-HT, agonists that have been used as pharmacological tools for investigating 5-HT3 receptor activity include 2-methyl-5-hydroxytryptamine (2-Me-5HT)3 and 1-(m-chlorophenyl)biguanide.4 More recently, 5-HT 3 receptor agonist activity has been reported for the imidazole 1,5 the N-(R)-3-quinuclidinyt benzoylurea 2,6 and a series of phenylureas derived from histamine as exemplified by 3. 7 While investigating structure-activity relationships among high affinity 5-HT3 receptor antagonists related to the 3-quinuclidinyl indole-3-carboxamide 4,2 we prepared the racemic indolyl-2 oxoacetamide 5 and determined that this compound had 5-HT3 receptor affinity comparable to 4.8, 9 However, further evaluation revealed two interesting facets relative to the progenitor 4: 1) a reversal in the enantioselectivity of the isomers of 5 for binding to the 5-HT3 receptor, and 2) both isomers of 5 were found to be 5-HT3 receptor partial agonists. Details of these findings are reported herein.