Abstract

Schizophrenia is a complex mental illness that affects almost 1% of the population and has no curative treatment. Currently, available neuroleptic drugs have severe limitations and induce drug-related adverse effects. Receptor binding affinity parameters and lipophilicity are important characteristics that describe the bioactivity of these drugs. Lipophilicity is an important physicochemical property of a drug, which predicts distribution, binding to plasma protein, crossing the blood–brain barrier, and biological activity. Five antipsychotic drugs (Haloperidol, Risperidone, Aripiprazole, Olanzapine, and Quetiapine) were selected and the experimental determination of lipophilicity was carried out by reverse phase thin-layer chromatography (RP-TLC) using four types of stationary phases (RP-18, CN, Diol, and NH₂ modified silica gel HPTLC plates) and acetonitrile-water with increasing percentage of acetonitrile and 0.2% formic acid in each case as mobile phase. Lipophilicity parameters (mR_M and R_M0) calculated from the experimental chromatographic retention data were discussed in terms of the correlation with different receptor binding affinity parameters determined by computational methods.

摘要

精神分裂症是一种复杂的精神疾病，影响着近 1% 的人口，并且没有治愈方法。目前，可用的精神抑制药物具有严重的局限性并会引起药物相关的不良反应。受体结合亲和力参数和亲脂性是描述这些药物生物活性的重要特征。亲脂性是药物的重要理化性质，它预测药物的分布、与血浆蛋白的结合、穿过血脑屏障和生物活性。选取氟哌啶醇、利培酮、阿立哌唑、奥氮平、喹硫平五种抗精神病药物，采用反相薄层色谱法（RP-TLC），使用四种固定相（RP-18、CN）进行亲脂性实验测定。 、二醇和 NH ₂改性硅胶 HPTLC 板）和乙腈-水，每种情况下乙腈和 0.2% 甲酸的百分比逐渐增加作为流动相。根据与通过计算方法确定的不同受体结合亲和力参数的相关性，讨论了根据实验色谱保留数据计算的亲脂性参数（mR _M和R _{M0 ）。}