Avram Speranta, Buiu Catalin, Duda-Seiman Daniel M, Duda-Seiman Corina, Mihailescu Dan
Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95, Splaiul Independentei, RO-76201, Bucharest, Romania.
Sci Pharm. 2010 Apr-Jun;78(2):233-48. doi: 10.3797/scipharm.0912-22. Epub 2010 May 5.
Antidepressants are psychiatric agents used for the treatment of different types of depression being at present amongst the most commonly prescribed drug, while their effectiveness and adverse effects are the subject of many studies and competing claims. Having studied five QSAR models predicting the biological activities of 18 antidepressants, already approved for clinical treatment, in interaction with the serotonin transporter (SERT), we attempted to establish the membrane ionsâ contributions (sodium, potassium, chlorine and calcium) supplied by donor/acceptor hydrogen bond character and electrostatic field to the antidepressant activity. Significant cross-validated correlation q(2) (0.5â0.6) and the fitted correlation r(2) (0.7â0.82) coefficients were obtained indicating that the models can predict the antidepressant activity of compounds. Moreover, considering the contribution of membrane ions (sodium, potassium and calcium) and hydrogen bond donor character, we have proposed a library of 24 new escitalopram structures, some of them probably with significantly improved antidepressant activity in comparison with the parent compound.
抗抑郁药是用于治疗不同类型抑郁症的精神药物，目前是最常处方的药物之一，而它们的有效性和副作用是许多研究和相互矛盾的说法的主题。在研究了五个预测已批准用于临床治疗的18种抗抑郁药与5-羟色胺转运体（SERT）相互作用的生物活性的定量构效关系（QSAR）模型后，我们试图确定由供体/受体氢键特征和静电场提供的膜离子（钠、钾、氯和钙）对抗抑郁活性的贡献。获得了显著的交叉验证相关系数q(2)（0.5至0.6）和拟合相关系数r(2)（0.7至0.82），表明这些模型可以预测化合物的抗抑郁活性。此外，考虑到膜离子（钠、钾和钙）的贡献以及氢键供体特征，我们提出了一个包含24种新艾司西酞普兰结构的库，其中一些与母体化合物相比可能具有显著提高的抗抑郁活性。
