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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.
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