Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Mar 17;34(2):387-92. doi: 10.1016/j.pnpbp.2010.01.005. Epub 2010 Jan 11.
Polymorphic multidrug resistant protein 1 (MDR1) transports drugs against a concentration gradient across the blood-brain barrier and reduces their accumulation in the brain. MDR1 may therefore influence antipsychotic brain availability contributing to inter-individual differences in treatment response and adverse effects, regardless of plasma concentrations. In the present study we investigated the influence of two common MDR1 polymorphisms on the improvement of psychopathological symptoms and occurrence of extrapyramidal side effects (EPS) in Slovenian schizophrenia patients acutely treated with risperidone. A total of 59 clinically well defined patients with first episode schizophrenia spectrum disorders or after tapering their maintenance treatment were genotyped for MDR1 C3435T and G2677T/A. Steady-state plasma concentrations of risperidone active moiety (sum of risperidone and the 9-hydroxyrisperidone) were determined. G2677T/A and C3435T genotypes were not associated to psychopathological symptoms, efficacy of treatment and risk for parkinsonism. Marginal associations with akathisia (p=0.039 and p=0.042, respectively) and dystonia (p=0.013 and p=0.034, respectively) were observed for both G2677T/A and C3435T genotypes. However, higher AIMS and BARS scores were observed only in heterozygous carriers of G2677T/A and C3435T polymorphisms and there was no tendency of gene-dose effect. The present study does not suggest a major influence of MDR1 G2677T/A and C3435T polymorphisms on treatment response during short-term risperidone therapy in patients with schizophrenia or schizoaffective disorder.
多药耐药蛋白 1（MDR1）多态性可将药物逆浓度梯度转运通过血脑屏障，并减少其在大脑中的积累。因此，MDR1 可能会影响抗精神病药物在大脑中的可用性，从而导致个体间治疗反应和不良反应的差异，而与血浆浓度无关。在本研究中，我们研究了两种常见的 MDR1 多态性对利培酮急性治疗的斯洛文尼亚精神分裂症患者的精神病理症状改善和锥体外系副作用（EPS）发生的影响。共有 59 例临床明确的首次发作精神分裂症谱系障碍或正在逐渐减少维持治疗的患者进行了 MDR1 C3435T 和 G2677T/A 的基因分型。测定了利培酮活性部分（利培酮和 9-羟基利培酮的总和）的稳态血浆浓度。G2677T/A 和 C3435T 基因型与精神病理症状、治疗效果和帕金森病风险无关。G2677T/A 和 C3435T 基因型与静坐不能（分别为 p=0.039 和 p=0.042）和肌张力障碍（分别为 p=0.013 和 p=0.034）均存在边缘相关性。然而，仅在 G2677T/A 和 C3435T 多态性的杂合子携带者中观察到 AIMS 和 BARS 评分较高，且没有基因剂量效应的趋势。本研究表明，MDR1 G2677T/A 和 C3435T 多态性在短期利培酮治疗精神分裂症或分裂情感障碍患者的治疗反应中没有主要影响。
