Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine.
Pharmacogenetic treatments for drug addiction: cocaine, amphetamine and methamphetamine.
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DOI：
10.1080/00952990902825447
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Kosten TA
中科院分区：
文献类型：
--
作者：
Haile CN;Kosten TR;Kosten TA
药物遗传学使用遗传变异来预测个体对药物的反应差异，并有望改善成瘾障碍的治疗。回顾基因变异如何影响对可卡因、安非他明和甲基苯丙胺的反应，以及这些信息如何指导药物治疗。我们进行了关于药物遗传学、可卡因、苯丙胺和甲基苯丙胺的交叉参考文献搜索。我们描述了多巴胺-β-羟基酶(D-βH)、儿茶酚-O-甲基转移酶(COMT)、多巴胺转运体(DAT1)、多巴胺D4受体和脑源性神经营养因子(BDNF)的功能遗传变异。DβH基因的单核苷酸多态(SNP；C-1021T)与可卡因成瘾的双硫仑药物治疗相关的偏执狂有关。具有SLC6A3基因3‘-非翻译区多态的个体对药物的反应发生改变。10/10重复对哌醋甲酯药物治疗的反应很差，9/9 DAT1变异体对苯丙胺表现出迟钝的兴奋和生理反应。COMT、D4受体和BDNF基因多态性与甲基苯丙胺滥用和精神病有关。通过分别考虑影响D、β、H和DAT1的基因多态性，优化了二硫仑和哌甲酸甲酯的可卡因成瘾药物治疗。在DAT1 VNTR变种中，苯丙胺的主观效应发生了改变，表明这是一种“受保护的”表型。以药物遗传学为基础的精神刺激成瘾治疗是成功治疗的关键。
Pharmacogenetics uses genetic variation to predict individual differences in response to medications and holds much promise to improve treatment of addictive disorders. To review how genetic variation affects responses to cocaine, amphetamine, and methamphetamine and how this information may guide pharmacotherapy. We performed a cross-referenced literature search on pharmacogenetics, cocaine, amphetamine, and methamphetamine. We describe functional genetic variants for enzymes dopamine-beta-hydroxylase (DβH), catechol-O-methyltransferase (COMT), and dopamine transporter (DAT1), dopamine D4 receptor, and brain-derived neurotrophic factor (BDNF). A single nucleotide polymorphism (SNP; C-1021T) in the DβH gene is relevant to paranoia associated with disulfiram pharmacotherapy for cocaine addiction. Individuals with variable number tandem repeats (VNTR) of the SLC6A3 gene 3′-untranslated region polymorphism of DAT1 have altered responses to drugs. The 10/10 repeat respond poorly to methylphenidate pharmacotherapy and the 9/9 DAT1 variant show blunted euphoria and physiological response to amphetamine. COMT, D4 receptor, and BDNF polymorphisms are linked to methamphetamine abuse and psychosis. Disulfiram and methylphenidate pharmacotherapies for cocaine addiction are optimized by considering polymorphisms affecting DβH and DAT1 respectively. Altered subjective effects for amphetamine in DAT1 VNTR variants suggest a ‘protected’ phenotype. Pharmacogenetic-based treatments for psychostimulant addiction are critical for successful treatment.
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