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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。
Genetic Pharmacology Use genetic tests to predict the effectiveness of drug treatment in individuals who are alcohol or opioid dependent. The common neurobiological basis for the potentiation and dependence of alcohol and opioids is to increase beta-endorphin release. Both the physiological and subjective effects of alcohol and opioids are closely linked to the β-endorphin and μ opioid receptors. Naltrexone therapy is a potent treatment of alcohol and opioid dependence that increases the basal release of beta-endorphin and thus inhibits the alcohol-induced further release of beta-endorphin. The role of naltrexone in the treatment of alcohol dependence is thought to be related to the functional single nucleotide polymorphism (SNP) of the mu opioid receptor gene (Al18G). Alcohol dependence patients with this single nucleotide polymorphism have a low recurrence rate after treatment with naltrexone. This single nucleotide polymorphism is more common among northerners in China, suggesting the importance of naltrexone in treating alcohol dependence in China. Another important genetic polymorphism associated with psychoactive substances or other drug dependence occurs in the promoter region encoding the dopamine β-hydroxylase (DβH) gene. This genetic polymorphism leads to a 10 -100-fold decrease in dopamine β-hydroxylase levels, converting dopamine in neurons to norepinephrine. Mental active substances with normal levels of dopamine β-hydroxylase depend on patients treated with dopamine β-hydroxylase inhibitors for significantly reduced drug abuse, whereas patients with low levels of dopamine β-hydroxylase are ineffective with this therapy. Genetic pharmacology has great potential for improving the therapeutic effect. We have identified genetic variants that can influence pharmacodynamics and pharmacokinetics. These variations guide the choice of drug treatment to optimize the treatment of alcohol and psychoactive substance abusers and reduce the rate of relapse after withdrawal.