PMID: 9170600Apr 1, 1997Paper

Single-dose toxicity studies of (+/-)-4-diethylamino-1, 1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence, in mice, rats and dogs

The Journal of Toxicological Sciences
Y NishiguchiN Sumi

Abstract

Comparative single-dose toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a new drug for the treatment of urinary frequency and incontinence, were conducted in ddY mice and Sprague-Dawley rats after oral(p.o.),intraperitoneal(i.p.) and subcutaneous(s.c.) administration, and in Beagle dogs after p.o. administration. The p.o. LD50 values of NS-21 were 852 and 1167 mg/kg for male and female mice, 2839 and 1739 mg/kg for male and female rats, respectively. The i.p. LD50 values were 324 and 390 mg/kg for male and female mice, and 423 and 359 mg/kg for male and female rats, respectively. No death occurred in mice and rats at doses up to s.c. 5000 mg/kg. Minimum lethal dose for dogs could not be determined because of vomiting. Mydriasis was noted in all three species tested without regard to administration route. In addition, decreased spontaneous locomotor activity, prone or lateral position, hypopnea, hypothemia, ataxic gait, twitch and clonic convulsion were observed in mice and rats after p.o. and i.p. administration. In rats, salivation was observed after p.o. administration and lacrimation was observed after p.o. and i.p. administration...Continue Reading

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