Antidiarrhoeal activity of new thiazolidinones related to loperamide

Abstract

A series of thiazolidinones related to loperamide was synthesized and evaluated for antidiarrhoeal activity in mice, using the castor oil test. Of five compounds tested, antidiarrhoeal activity was found only for 2-(p-nitrophenyl)-3-{3-[(4-(p-chlorophenyl)-4-hydroxy)piperidino] ethyl}1,3-thiazolidin-4-one. The compound was less active than loperamide (ED50 values =48.7 (24.8-95.6) and 0.91 (0.24-3.40) mg kg-1 respectively) but was also less toxic (LD50 values 745.9 (545.2-929.8) and 108.9 (85.5-138.7) mg kg-1, respectively). Its antidiarrhoel activity was countered by naloxone. Our results support the hypothesis that this compound, like loperamide, is an opiate-receptor agonist.