CAJ | 학술논문

遗传药理学使用基因检测的方法预测药物治疗对酒精或阿片类物质依赖患者个体的有效性.酒精和阿片类物质产生强化效应和依赖的共同神经生物学基础是增加β-内啡肽释放.酒精和阿片类物质引起的生理和主观效应都与β-内啡肽和μ阿片受体有密切的关系.纳曲酮治疗是一种对酒精和阿片依赖均有效的治疗方法,其能增加β- 内啡肽的基础释放量,从而抑制酒精引起的β-内啡肽进一步释放.纳曲酮在治疗酒精依赖中的作用被认为与μ阿片受体基因(Al18G)的功能性单核苷酸多态性(SNP)有关.具有这种单核苷酸多态性的酒精依赖患者使用纳曲酮治疗后复发率低.这种单核苷酸多态性在中国北方人中较为常见,因此提示了纳曲酮治疗酒精依赖在中国的重要性.另一个与精神活性物质或其他药物依赖相关的重要基因多态性多发生于编码多巴胺β-羟化酶(DβH) 基因的启动子区域.这种基因多态性可导致多巴胺β-羟化酶水平降低10-100倍,使神经元中的多巴胺转化为去甲肾上腺素.多巴胺β-羟化酶水平正常的精神活性物质依赖患者采用多巴胺β-羟化酶抑制剂治疗能明显减少药物滥用,而多巴胺β-羟化酶水平低的患者采用该疗法治疗无效.遗传药理学在改善治疗效果方面有巨大的潜力.我们已经鉴别出能影响药效学和药代动力学因素的基因变异体.这些变异能够指导药物治疗的选择,使酒精和精神活性物质滥用患者得到最优化的治疗,降低戒断后的复吸率.
유전약이학사용기인검측적방법예측약물치료대주정혹아편류물질의뢰환자개체적유효성.주정화아편류물질산생강화효응화의뢰적공동신경생물학기출시증가β-내배태석방.주정화아편류물질인기적생리화주관효응도여β-내배태화μ아편수체유밀절적관계.납곡동치료시일충대주정화아편의뢰균유효적치료방법,기능증가β- 내배태적기출석방량,종이억제주정인기적β-내배태진일보석방.납곡동재치료주정의뢰중적작용피인위여μ아편수체기인(Al18G)적공능성단핵감산다태성(SNP)유관.구유저충단핵감산다태성적주정의뢰환자사용납곡동치료후복발솔저.저충단핵감산다태성재중국북방인중교위상견,인차제시료납곡동치료주정의뢰재중국적중요성.령일개여정신활성물질혹기타약물의뢰상관적중요기인다태성다발생우편마다파알β-간화매(DβH) 기인적계동자구역.저충기인다태성가도치다파알β-간화매수평강저10-100배,사신경원중적다파알전화위거갑신상선소.다파알β-간화매수평정상적정신활성물질의뢰환자채용다파알β-간화매억제제치료능명현감소약물람용,이다파알β-간화매수평저적환자채용해요법치료무효.유전약이학재개선치료효과방면유거대적잠력.아문이경감별출능영향약효학화약대동역학인소적기인변이체.저사변이능구지도약물치료적선택,사주정화정신활성물질람용환자득도최우화적치료,강저계단후적복흡솔.
Pharmacogenetics uses genetic tests to predict the effectiveness of medication treatments for individual patients with drug dependence such as alcohol and opiates. An important shared neurobiological component of the reinforcement and dependence on alcohol and opiates is alcohol's enhancement of β-endorphin release. The physiological and subjective effects of both alcohol and opiates are associated with β-endorphin and the mu opiate system. A pharmacotherapy that has been effective for both disorders is naltrexone, which increases baseline β-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters its receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. This SNP is particularly common among northern Chinese suggesting an important role for naltrexone treatment of alcoholism in China. Another important genetic polymorphism related to stimulant and perhaps other types of dependence frequently occurs (about 40% of the population) in the promoter region of the gene coding for dopamine beta hydroxylase (DβH). This polymorphism leads to 10 to 100 times lower levels of the DβH enzyme, which converts dopamine to norepinephrine in neurons. Stimulant abusers with normal levels of this enzyme show significant reductions in stimulant abuse when treated with DβH inhibitors, while those with the polymorphism for low DβH levels show no treatment efficacy with these medications. Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic as well as the more commonly studied pharmacokinetic factors. These mutations can guide pharmacotherapeutic agent choice for optimum treatment of alcohol and stimulant abuse and reduce relapse after successful initial abstinence.