Pharmacological properties of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent.
1-(2',6'-Dimethylphenyl)-3-amidinourea hydrochloride (WHR-1142A, lidamidine hydrochloride), a potent, unique antidiarrheal agent, was tested for other pharmacological properties. It inhibited gastric acid secretion in both 4-h and 22-h pylorus-ligated rats and reduced mortality and gastric ulcer severity in the latter test. WHR-1142A also exhibited local anesthetic activity in the rabbit corneal reflex and guinea pig intradermal wheal tests and reverisbly blocked conduction in isolated frog nerves. Low doses of WHR-1142A increased plasma glucose concentration in fasted mice and rats and prolonged the hyperglycemia in response to a glucose meal. WHR-1142A showed mild diuretic activity but had no anti-inflammatory or antibacterial activity. The acute oral LD50 of WHR-1142A was 260 (208,328) mg/kg in male mice, 267 (212,336) mg/kg in male rats and 160 130,197) mg/kg in female rats.
D000578:Amidines / Q000494:pharmacology*; D000779:Anesthetics, Local; D000818:Animals; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000930:Antidiarrheals / Q000494:pharmacology*; D001001:Anura; D001419:Bacteria / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D004232:Diuretics; D005750:Gastric Juice / Q000378:metabolism; D005951:Glucose Tolerance Test; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects; D012882:Skin Tests
D000578:Amidines; D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D000897:Anti-Ulcer Agents; D000930:Antidiarrheals; D001786:Blood Glucose; D004232:Diuretics