双重作用的多巴胺D2/5-HT2A受体拮抗剂比较药效团分析

双重作用的多巴胺D₂/5-HT_2A受体拮抗剂是开发非典型抗精神病药物的有效途径，但最新研究显示, 非典型抗精神病药物将显著增加患者因心律失常及其他心脏疾病而猝死的风险，本文对D₂/5-HT_2A受体拮抗剂的药效团模型以及可能引起心血管风险的α_1A肾上腺素受体拮抗剂和hERG K⁺通道阻断剂的药效团模型进行比较分析，从药效团模型的角度分析多靶点药物的设计。

Comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists

Dual dopamine D₂/5-HT_2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms.  However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk.  In this paper, comparative pharmacophore analysis of dual dopamine D₂/5-HT_2A receptor antagonists, hERG K⁺ channel blockers, and α_1A adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.