George M. Luke

Potential non-dopaminergic gastrointestinal prokinetic agents in the series of substituted benzamides

Abstract A series of 2-substituted-4-amino-5-chloro-N-[2-diethylaminoethyl]benzamides was synthesized and evaluated for gastrointestinal motility enhancing activity in vitro (enhancement of field stimulated guinea pig ileum test) and in vivo (enhancement of rat stomach emptying). A number of compounds were shown to be potent gastrointestinal prokinetic agents yet were devoid of dopaminergic D2-receptor antagonism as shown by their inability to displace [3H]spiperone from brain membranes. The model compound 6b would be expected to have clinical use in a spectrum of upper gastroinstestinal motility disorders but without the central nervous system side effects characteristic of dopaminergic D2-receptor blockade in the brain.