Lytton William W
Dept. Physiology & Pharmacology, SUNY Downstate, Brooklyn, NY.
Dept. Neurology, SUNY Downstate, Brooklyn, NY.
Drug Discov Today Dis Models. 2016 Spring;19:27-30. doi: 10.1016/j.ddmod.2017.02.007. Epub 2017 Jun 3.
Analysis of the brain as a dynamical system can assist drug development for dynamical diseases such as epilepsy. The pathological trajectories that make up a seizure differ significantly from the physiological trajectories of normal brain function. These trajectories depend on parameters - conductances and time constants of ion channels and synapses - that can be modified by drugs. Drug development will benefit by taking account of the way in which multiple parameters - multiple drug targets - produce trajectory alterations. This may lead us to reconsider potential benefits of multi-target polypharmacy, of drug cocktails, and of so-called "dirty drugs" (drugs with activity at multiple locations).
将大脑视为一个动态系统进行分析,有助于针对癫痫等动态疾病开展药物研发。构成癫痫发作的病理轨迹与正常脑功能的生理轨迹有显著差异。这些轨迹取决于一些参数——离子通道和突触的电导及时间常数——而药物可以对这些参数进行调节。通过考虑多个参数(多个药物靶点)产生轨迹改变的方式,药物研发将从中受益。这可能会促使我们重新审视多靶点复方药物、药物鸡尾酒以及所谓“脏药物”(在多个位点具有活性的药物)的潜在益处。