[Reproductive and developmental 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 (3). Teratogenicity study in rabbits by oral administration].
A study of the effect 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, was conducted in New Zealand White rabbits during the period of fetal organogenesis. Female rabbits were given NS-21 orally at dose levels of 0 (control), 2, 10 and 50 mg/kg from day 6 to day 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. Five does in the 10 mg/kg dosage group and one doe in the 50 mg/kg dosage group died or were sacrificed in moribund condition. Two does in the control group died. Lacrimation and convulsion were observed in the 10 and 50 mg/kg groups, and no or soft stool was observed in the 50 mg/kg dosage group. Body weight gain, food and water consumptions were decreased in the 50 mg/kg dosage group. There were no effects of NS-21 in necropsy findings at cesarean sections in does at any dosage level. Developmental toxicity of fetuses was not apparent at any dosage level. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 2 mg/kg for maternal toxicity and 50 mg/kg for fetal toxicity.
Schardein
J L
JL
MPI Research (Formerly International Research and Development Corporation) Mattawan, Michigan 49071, USA.
York
R G
RG
Ninomiya
H
H
Watanabe
M
M
Sumi
N
N
D000284:Administration, Oral; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D008297:Male; D015394:Molecular Structure; D010648:Phenylacetates / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D011247:Pregnancy; D011817:Rabbits; D012098:Reproduction / Q000187:drug effects; D013723:Teratogens / Q000737:chemistry / Q000633:toxicity*; D014549:Urinary Incontinence / Q000188:drug therapy; D014555:Urination Disorders / Q000188:drug therapy*
D010648:Phenylacetates; D013723:Teratogens; C105354:temiverine