Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice.
Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice.
复制标题
戊诺酰胺、利培酮和奥氮平对小鼠的致畸性比较分析。
DOI：
10.1111/bdi.12325
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发表时间：
2015
影响因子：
5.4
通讯作者：
Finnell,RichardH
中科院分区：
文献类型：
--
作者：
Wlodarczyk,BogdanJ;Ogle,Krystal;Lin,LindaYing;Bialer,Meir;Finnell,RichardH
ObjectivesBased on the recent findings from animal studies, it has been proposed that the therapeutic use of valnoctamide, an anxiolytic drug developed in the early 1960s, be extended to treat other neurological disorders such as epilepsy and bipolar disease. Given the scarcity of adequate data on its prenatal toxicity, a comparative teratogenicity study of valnoctamide and two of the most commonly used drugs to treat bipolar disorder, risperidone and olanzapine, was carried out in a mouse model system.MethodsPregnant dams were treated with the aforementioned three drugs at the dose levels calculated as an equal proportion of the respective LD50values of these drugs. The main reproductive indices examined included the numbers of implantations and resorptions, viable and dead fetuses, and fetal gross, visceral and skeletal abnormalities.ResultsThe outcomes of the present study indicated that olanzapine was the most teratogenic of the three drugs, inducing maternal‐, embryo‐, and fetotoxicity. Risperidone also exerted a significant prenatal toxicity, but its adverse effect was less pronounced than that induced by olanzapine. Valnoctamide did not show any teratogenic effect, even when used in relatively higher dosages than olanzapine and risperidone. The observed increased skeletal abnormalities in one of the valnoctamide treatment groups were nonspecific and, as such, signaled a modest developmental delay rather than an indication that the compound could induce structural malformations.ConclusionsUnder our experimental conditions, valnoctamide demonstrated the lowest prenatal toxicity of the three tested drugs.
