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首页> 外文期刊>Alcohol >Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: Exploratory findings
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Ondansetron and sertraline may interact with 5-HTTLPR and DRD4 polymorphisms to reduce drinking in non-treatment seeking alcohol-dependent women: Exploratory findings

机译：恩丹西酮和舍曲林可能与5-HTTLPR和DRD4多态性相互作用，以减少非治疗性酒精依赖妇女的饮酒：探索性发现

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The purpose of this exploratory study was to examine the interaction of 5-HTTLPR and DRD4 exon III polymorphisms with gender in non-treatment seeking alcohol-dependent (AD) individuals while alternately taking ondansetron and sertraline. Evidence suggests that alcohol dependence may be influenced by a genetic interaction that may be gender-specific with temporal changes making pharmacological treatment with serotonergic drugs complex. The main trial was a within-subject double-blind placebo-controlled human laboratory study with 77 non-treatment-seeking AD individuals randomized (55 completed, 49 complete data) to receive 200mg/day of sertraline or 0.5mg/day of ondansetron for 3 weeks followed by an alcohol self-administration experiment (ASAE), then placebo for 3 weeks followed by a second ASAE, then receive the alternate drug, in a counterbalanced order, for 3 weeks followed by a third ASAE. Results for men were not significant. Women with the LL 5-HTTLPR genotype receiving ondansetron and SS/SL 5-HTTLPR genotype receiving sertraline (matched), drank significantly fewer drinks per drinking day (DDD) during the 7 days prior to the first and third ASAEs than women receiving the mismatched medication (i.e., sertraline to LL and ondansetron to SS/SL). In a 3-way interaction, 5-HTTLPR alleles by DRD4 alleles by medications, women with the LL genotype who received ondansetron and had DRD4 ≥7 exon III repeats drank significantly fewer DDD as did SS/SL women who received sertraline but conversely had DRD4 <7 repeats in the 7-day period leading up to the first and third ASAEs. Consistent with these data was a significant reduction of milliliters consumed ad libitum during these same ASAEs. These exploratory findings add possible support to gender and genetic differences among AD individuals in response to serotonergic pharmacotherapies. Future trials should be powerful enough to take into account that endophenotypes and a targeting of serotonergic interactions may be essential to successfully treat alcohol dependence.
机译：这项探索性研究的目的是在非治疗性寻求酒精依赖（AD）个体的情况下，检查5-HTTLPR和DRD4外显子III多态性与性别的相互作用，同时服用恩丹西酮和舍曲林。有证据表明，酒精依赖可能受到遗传相互作用的影响，遗传相互作用可能随性别而异，随时间的变化而使血清素能药物的药理学治疗变得复杂。主要试验是一项在受试者内部进行的双盲安慰剂对照人类实验室研究，该研究对77位非治疗性AD患者进行了随机分组（55例完成，49例完整数据），接受200毫克/天的舍曲林或0.5毫克/天的恩丹西酮治疗。 3周，然后进行酒精自我管理实验（ASAE），然后进行安慰剂治疗3周，然后进行第二次ASAE，然后以平衡的方式接受替代药物治疗3周，然后进行第三次ASAE。男性结果并不显着。接受恩丹西酮的LL 5-HTTLPR基因型和接受舍曲林（匹配）的SS / SL 5-HTTLPR基因型的妇女，在第一次和第三次ASAE之前的7天内，每天的饮酒量（DDD）比接受不匹配的妇女少药物（即舍曲林至LL，恩丹西酮至SS / SL）。在三向相互作用中，药物治疗的DRD4等位基因与5-HTTLPR等位基因，接受恩丹西酮且DRD4≥7外显子III重复的LL基因型女性的DDD明显少于接受舍曲林但反之具有DRD4的SS / SL妇女在7天内重复<7次，直到出现第一个和第三个ASAE。与这些数据一致的是，在这些相同的ASAE期间，随意摄入的毫升数显着减少。这些探索性发现为响应血清素能药物疗法的AD个体之间的性别和遗传差异提供了可能的支持。未来的试验应足够强大，以考虑到内表型和血清素能相互作用的靶向对于成功治疗酒精依赖可能至关重要。

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