Tong Junchao, Mizrahi Romina, Houle Sylvain, Kish Stephen J, Boileau Isabelle, Nobrega Jose, Rusjan Pablo M, Wilson Alan A
Research Imaging Centre, Centre for Addiction and Mental Health, Campbell Family Mental Health Research Institute, Toronto, ON, Canada.
J Cereb Blood Flow Metab. 2017 Nov;37(11):3635-3639. doi: 10.1177/0271678X16668890. Epub 2016 Oct 1.
In a recent clinical trial, the drug BIA 10-2474, a putative fatty acid amide hydrolase(FAAH) inhibitor, was responsible for severe adverse events (SAEs), including one death. To date, there has been little reliable information divulged about the potency of BIA 10-2474 at FAAH in the central nervous system. We synthesised BIA 10-2474 and determined its ability to inhibit FAAH ex vivo in rat brain using a FAAH selective radiotracer. BIA 10-2474 proved to be a potent FAAH inhibitor with ICs of 50-70 µg/kg (i.p.) in various brain regions. This information may be useful for determining the cause of the SAEs.
在最近的一项临床试验中，药物BIA 10-2474（一种假定的脂肪酸酰胺水解酶（FAAH）抑制剂）导致了严重不良事件（SAE），包括1例死亡。迄今为止，关于BIA 10-2474在中枢神经系统中对FAAH的抑制效力，几乎没有可靠信息公布。我们合成了BIA 10-2474，并使用FAAH选择性放射性示踪剂在大鼠脑内体外测定其抑制FAAH的能力。结果证明，BIA 10-2474是一种强效FAAH抑制剂，在各个脑区腹腔注射时的半数抑制浓度（IC50）为50 - 70μg/kg。该信息可能有助于确定严重不良事件的原因。
