Vanoxerine国家药物滥用研究所。

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Vanoxerine国家药物滥用研究所。

当今Investig药物。2000年10月,1 (2):241 - 51。

PubMed ID
11249581 (在PubMed
]
文摘

Vanoxerine (gbr - 12909)是一个合成的高亲和性多巴胺再摄取抑制剂在1970年代末,最初在欧洲测试作为一个潜在的抗抑郁药。1989年,建议gbr - 12909可能有用的治疗可卡因成瘾[346980]。该药物已完成第一阶段临床试验由美国国家药物滥用研究所的潜在治疗可卡因滥用(346245、376621)。多剂量、安全性和药物动力学、非盲、顺序固定dose-escalating研究已经完成。四个剂量的vanoxerine健康正常的志愿者管理,评估药物的安全性和耐受性在25,75和100毫克。进一步发展有可能继续,等待审查的数据[376621]。多巴胺转运体入住率也被测量。经过2周的剂量在75或100毫克口服vanoxerine 8人类受试者,随后的PET扫描初步结果表明,入住率增加剂量,达到25 - 35% 100毫克[346245]。在这些剂量,药物没有造成行为症状如可卡因,这表明药物没有滥用潜力。如果没有出现安全问题,复合与cocaine-dependent科目将在试验评估,连同它的导数,化合物5 [346980]。 It is thought that prolonged treatment with vanoxerine could reverse the addiction process, following studies in rats showing that dopamine transporter levels returned to normal when animals were switched to vanoxerine therapy immediately after cocaine administration [346980]. Vanoxerine has an affinity constant (Ki), at the human dopamine transporter, of 9 nM [347021]. Gist-Brocades originally initiated studies of vanoxerine, along with another piperazine, GBR-12935, for the treatment of cocaine dependence. The company was also investigating vanoxerine as a potential antipsychotic therapeutic agent; development for this indication has been discontinued [190331]. In 1995, the NIDA began to fund studies into the potential of vanoxerine to reduce cocaine self-administration by rhesus monkeys. Early data showed that vanoxerine could decrease cocaine-maintained responding (CMR) in rhesus monkeys, without affecting similar levels of food-maintained responding (FMR). Furthermore, a decanoate ester of a hydroxylated analog of vanoxerine, DBL-583, could decrease CMR by 80% while leaving FMR unaffected; this effect lasted almost 30 days with a single injection [227488,346980]. Similar studies have shown that, by inhibiting the dopamine transporter, for which vanoxerine has a 500-fold increased affinity in comparison to cocaine, vanoxerine could selectively reduce(1 mg/kg i.v.) or eliminate (3 mg/kg i.v.) cocaine self-administration in primates. The drug was well tolerated with no changes in blood pressure or oxygen saturation. Oral administration of the drug in clinical trials was planned following this study [346990].

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药物
药物靶点
药物 目标 类 生物 药理作用 行动
Vanoxerine Sodium-dependent多巴胺转运体 蛋白质 人类
是的
拮抗剂
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