关键词: 5-羟色胺, 去甲肾上腺素, 药效团模型, 双重重摄取抑制剂

The biogenic amine transmitters serotonin and norepinephrine have been linked to depression. Pharmacophore models were developed by using Catalyst Hypogen program with a training set of 22 5-HT reuptake inhibitors and 19 NE reuptake inhibitors, which were carefully selected with great diversity in both molecular structure and bioactivity for discovering new potent serotonin/norepinephrine reuptake inhibitors. The best 5-HT pharmacophore hypothesis (Hypo1), has a correlation coefficient of 0.935. The best NE pharmacophore hypothesis (Hypo1), has a correlation coefficient of 0.844, suggesting that a highly predictive 5-HT and NE pharmacophore models were successfully obtained. The predictive ability was approved by the results of the activity estimated by mapping the compounds of the training and testing sets with pharmacophore models. The results of our study provide a valuable tool in designing new leads with desired biological activity by virtual screening.

Key words: serotonin, norepinephrine, pharmacophore model, dual reuptake inhibitors