In 2016 one person died and others had neurological sequelae during a clinical trial with BIA 10-2474 (3-(1-(cyclohexyl(methyl)carbamoyl)-lH-imidazol-4-yl)pyridine 1-oxide), a novel fatty acid amide hydrolase (FAAH) inhibitor being developed for the treatment of medical conditions such as pain. Prior to the clinical trial a full battery of regulatory toxicology tests were carried out and this paper describes the genotoxicity/mutagenicity tests undertaken with BIA 10-2474 using the Ames (Salmonella typhimurium) reverse mutation test, the Escherichia coli WP2uvrA forward mutation test, an in vitro chromosome damage assay in human lymphocytes, and an in vivo micronucleus test in mice. All tests were conducted with and without a rat liver S9 metabolic activation system. None of the test results were judged to be positive with regards to the mutagenicity/genotoxicity of BIA 10-2474 making it unlikely that any such effect was involved in the toxicity observed in the clinic.

中文翻译：

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没有新的脂肪酸酰胺水解酶抑制剂BIA 10-2474的遗传毒性。

在2016年，有人用BIA 10-2474（一种新型脂肪3-（1-（1-（环己基（甲基）氨基甲酰基）-1H-咪唑-4-基）吡啶1-氧化物）进行了临床试验，一个人死亡，其他人患有神经系统后遗症。酸性酰胺水解酶（FAAH）抑制剂正在开发中，用于治疗诸如疼痛之类的医学疾病。在进行临床试验之前，已进行了一系列全面的毒理学测试，本文介绍了使用Ames（鼠伤寒沙门氏菌）反向突变测试，大肠杆菌WP2uvrA正向突变测试，BIA 10-2474进行的遗传毒性/诱变测试。人淋巴细胞的体外染色体损伤测定和小鼠的体内微核试验。所有测试均在有和没有大鼠肝S9代谢激活系统的情况下进行。