非人灵长类动物的发育神经毒性评价方法

Evaluation methods for developmental neurotoxicity of nonhuman primates

药物的非临床发育神经毒性(Developmental neurotoxicity,DNT)研究是药物非临床安全性评价的重要组成部分,通常与生殖发育毒性(Developmental And Reproductive Toxicity,DART)研究相结合。由于大分子生物技术药物多具有高度的种属特异性,在大鼠和兔体内不能或较少产生药理学应答,因此生物技术药物在评价DART时往往使用与人类更为接近的非人灵长类动物(Non-human Primates,NHPs)。非人灵长类动物的生理特征与人类高度类似,行为高度进化,具有高级的解决问题的能力及复杂的社会关系,因此特别适合用于生物技术药物的非临床DNT研究。本文综述了非人灵长类动物的发育神经毒性评价方法,为评价非人灵长类的神经行为学提供了概况,以期更好的研究药物的发育神经毒性。

The study for nonclinical developmental neurotoxicity （DNT） of drugs is an important part of the nonclinical safety evaluation. It is often combined with the study of developmental and reproductive toxicity （DART）. Most biopharmaceuticals are highly species-specific and can not interact with rats or rabbits, while non- human primates are more similar to humans. Thus, non-human primates are preferred in DART evaluation of biop- harmaceuticals. The physiological characteristics of non-human primates are highly similar to humans, and the be- havioral repertoire of non-human primates is highly evolved, for example, advanced problem-solving capabilities and complex social relationships. This similarity makes non-human primates valuable animal models for DNT studies. This review described tests designed to study developmental neurotoxicity of non-human primates, providing a rough framework of non-human primate neurobehavioral, in order to study developmental neurotoxicity of drugs better.