现有临床抗抑郁药物多以单胺为靶标设计,单胺重摄取抑制剂仍是抗抑郁新药研发的热点方向。新药研发周期长,投资高,风险大,如何快速准确完成药物筛选和临床前评价至关重要。该课题组采用体外高通量筛选和整体动物药效学验证相结合的评价模式,建立了单胺重摄取抑制剂评筛体系,该体系的建立将对单胺重摄取抑制剂的快速评价产生推动作用,也有助于挖掘新的研究思路。该文围绕抗抑郁药效学评价、作用靶标研究、单胺递质含量检测及神经元电活动研究对单胺重摄取抑制剂的评价策略和体系作一综述。
Currently,commercially available antidepressants are synthetized targeting at monoamine system,and development of new monoamine reuptake inhibitors is still be of great interest for researchers.It is well known that new drug development needs great investment and long term studies,and is accompanied by high risk.So it is necessary and important to perform screening for potential monoamine inhibitors faster.Following long term effort and practice,our team established a series of strategies and an integrated system for antidepressant screening and evaluation of monoamine reuptake inhibitors,combining high throughput screening technology and in vivo animal tests together.Here,we review the strategies and system for antidepressants screening and evaluation,focusing on pharmacodynamic evaluation,target studies and monoamine determination.