Chamorro G, Martínez M, Salazar M, Salazar S, Hong E
Departamento de Toxicología, Escuela Nacional de Ciencias Biológicas, I.P.N., México, D.F.
Arch Inst Cardiol Mex. 1995 Jul-Aug;65(4):300-6.
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.
吲哚那酯（TR3369）是一种新型抗高血压药物，通过口服给药，以0、10、20、40和60毫克/千克/天的剂量对大鼠进行了一般生殖性能、围产期和胚胎胎儿毒性研究。在生育力研究中，除60毫克/千克剂量外，任何剂量均未导致亲代体重增加、生育力、胎儿体重或存活率下降。未观察到表面翻正、耳廓展开或惊吓反应延迟。另一方面，40和60毫克/千克显著增加了吸收数量。在围产期研究中，40和60毫克/千克的剂量增加了出生时死胎的数量，后者还影响了存活率、生长和空气翻正反射。F1代后代的生殖性能未受损害。与作为其结构衍生物的血清素不同，吲哚那酯在器官发生期给药时未显示致畸性证据。得出的结论是，高达20毫克/千克的剂量不会影响胎儿发育参数，这一剂量约为高血压患者建议剂量的1200倍。
