Mechanism of action studies of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent.
1-(2,6-Dimethylphenyl)-3-methylamidinourea hydrochloride (WHR-1142A), lidamidine hydrochloride), a novel antidiarrheal agent, inhibited contractile activity in isolated guinea pig ileum stimulated by acetylcholine, histamine, serotonin, dimethylphenylpiperazinium, prostaglandin E2, BaCl2 and KCl. WHR-1142A also blocked spontaneous and stimulated contractile activity measured with extraluminal strain gauges in the duodenum, ileum and colon of dogs. Studies on the autonomic effects of WHR-1142A indicated little, if any, peripheral adrenergic stimulatory or cholinergic blocking activity. Inhibition of intestinal motility by WHR-1142A was not antagonized by naloxone. WHR-1142A also showed no morphine-like analgesic effects and was devoid of any H1-antihistamine activity. WHR-1142A appears to be a pharmacologically unique antidiarrheal agent.
D000578:Amidines / Q000494:pharmacology*; D000700:Analgesics; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D001337:Autonomic Agents; D004157:Diphenoxylate / Q000494:pharmacology; D004285:Dogs; D004386:Duodenum / Q000187:drug effects; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists; D006636:Histamine Release / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D011817:Rabbits
D000578:Amidines; D000700:Analgesics; D000930:Antidiarrheals; D001337:Autonomic Agents; D006634:Histamine H1 Antagonists; D009270:Naloxone; D004157:Diphenoxylate