Martin R A, de la Iglesia F A
Am J Cardiol. 1987 Jun 15;59(16):10H-14H. doi: 10.1016/0002-9149(87)90138-x.
Pirmenol hydrochloride, a novel pyridinemethanol derivative, is a long-acting class Ia antiarrhythmic agent. Preclinical toxicology data were obtained in rat, mouse, dog and rabbit. In acute toxicity studies by oral and intravenous routes, no pathologic changes were observed in surviving mice, rats and dogs. In repeated dose toxicity studies, no drug-related pathologic changes were evident; dryness of the oral mucosa in dogs and body weight gain reductions in rodents were the only significant clinical signs. In a chronic (52 week) toxicity study in rats, pirmenol given in the diet was tolerated clinically at doses up to 100 mg/kg/day. No drug-related aberrations in clinical laboratory parameters or ophthalmic or pathologic findings were evident. In a similar study in beagle dogs, pirmenol was tolerated clinically at a dosage up to 30 mg/kg/day. No significant changes in biochemical, hematologic, urinary or bone marrow determinations were found in either species. In reproductive toxicology studies in rats, pirmenol had no significant effect on litter size or embryonic viability. In rabbits pirmenol had no effect on average litter size, embryonic viability or fetal wastage. Given to male rats, pirmenol had no overt effects on fertility. Pirmenol failed to elicit deoxyribonucleic acid damage or induce cytogenetic alterations. Pirmenol appears to be without significant limiting toxicologic properties.
盐酸哌莫洛尔是一种新型吡啶甲醇衍生物，是一种长效Ia类抗心律失常药物。在大鼠、小鼠、犬和兔身上获得了临床前毒理学数据。在经口和静脉途径的急性毒性研究中，存活的小鼠、大鼠和犬未观察到病理变化。在重复给药毒性研究中，未发现与药物相关的病理变化；犬的口腔黏膜干燥和啮齿动物体重增加减少是唯一显著的临床体征。在大鼠的慢性（52周）毒性研究中，饮食中给予高达100mg/kg/天剂量的哌莫洛尔在临床上是可耐受的。临床实验室参数、眼科或病理检查结果均未发现与药物相关的异常。在比格犬的类似研究中，哌莫洛尔在高达30mg/kg/天的剂量下在临床上是可耐受的。两种动物的生化、血液学、尿液或骨髓检测均未发现显著变化。在大鼠的生殖毒理学研究中，哌莫洛尔对窝仔数或胚胎活力没有显著影响。在兔身上，哌莫洛尔对平均窝仔数、胚胎活力或胎儿丢失没有影响。给予雄性大鼠，哌莫洛尔对生育能力没有明显影响。哌莫洛尔未引起脱氧核糖核酸损伤或诱导细胞遗传学改变。哌莫洛尔似乎没有显著的限制毒性特性。
