Effects of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent on the cardiovascular and central nervous systems.
1-(2,6-Dimethylphenyl)-3-methylamidinourea hydrochloride (WHR-1142A, lidamidine hydrochloride) has been reported to be a potent antidiarrheal agent in laboratory animals. This study defines its effects on the cardiovascular and central nervous systems. At doses greater than 1 mg/kg i.v., WHR-1142A reduced cardiac output in the anesthetized dog primarily by depressing heart rate; the blood pressure was slightly elevated due to an increase in peripheral resistance. WHR-1142A was effective in reverting ouabain-induced ventricular arrhythmias to a sinus rhythm. Unlike diphenoxylate, WHR-1142A did not potentiate the CNS depressant effects of hexobarbital or ethanol. WHR-1142A did not block pentetrazole-induced convulsions, electroshock seizures or amphetamine aggregate toxicity. At high doses WHR-1142A caused a general CNS depressant effect was not related to a neuroleptic- or barbiturate-like action.
D000578:Amidines / Q000494:pharmacology*; D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology; D005479:Flurazepam / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects
D000578:Amidines; D000930:Antidiarrheals; D000431:Ethanol; D006591:Hexobarbital; D000661:Amphetamine; D005479:Flurazepam; D010433:Pentylenetetrazole