[Evaluation of the toxicity of indorenate on reproduction].
Indorenate (TR3369) a new antihypertensive drug, was examined for effects upon general reproductive performance, for peri-postnatal and embryofetal toxicity in the rat at doses of 0, 10, 20, 40 and 60 mg/kg/day by oral administration. Excluding the 60 mg/kg dose, in the fertility study, any dose produced neither decrement of body weight gain of progenitors, fertility, fetal weight nor survival rate. Retardation of the surface righting, pinnal unfolding or startle response were not observed. On the other hand, 40 and 60 mg/kg significantly increased the number of resorptions. In the peri-postnatal study, doses of 40 and 60 mg/kg incremented the number of dead pups at birth, and the later also affected the survival rate, growing and air righting reflex. Reproductive performance of the F1 offsprings was unimpaired. Indorenate in contrast to serotonin, from which it is a structural derivative, gave no evidence of teratogenicity when administered during the period of organogenesis. It was concluded that the parameters of fetal development were not affected by doses of up to 20 mg/kg, which represents approximately 1200 times the proposed dose for hypertensive patients.
Chamorro
G
G
Departamento de Toxicología, Escuela Nacional de Ciencias Biológicas, I.P.N., México, D.F.
Martínez
M
M
Salazar
M
M
Salazar
S
S
Hong
E
E
D008735:5-Methoxytryptamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005313:Fetal Death / Q000139:chemically induced; D005333:Fetus / Q000187:drug effects*; D008297:Male; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000187:drug effects*
D000959:Antihypertensive Agents; D008735:5-Methoxytryptamine; C033600:indorenate
Evaluación de la toxicidad del indorrenato sobre la reproduccion.