Antidiarrhoeal activity of new thiazolidinones related to loperamide.
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 antidiarrhoeal activity was counteracted by naloxone. Our results support the hypothesis that this compound, like loperamide, is an opiate-receptor agonist.
Diurno
M V
MV
Department of Pharmaceutical Chemistry, University of Naples Federico II, Italy.
Izzo
A A
AA
Mazzoni
O
O
Bolognese
A
A
Capasso
F
F
D000818:Animals; D000930:Antidiarrheals / Q000627:therapeutic use*; D002368:Castor Oil / Q000633:toxicity; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy*; D007928:Lethal Dose 50; D008139:Loperamide / Q000031:analogs & derivatives* / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology
D000930:Antidiarrheals; D009292:Narcotic Antagonists; D009270:Naloxone; D008139:Loperamide; D002368:Castor Oil