D3R部分激动剂BP 897可减弱可卡因和d -安非他明的区别性刺激作用,不能自行给药

P. Beardsley, P. Sokoloff, R. Balster, J. Schwartz
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引用次数: 56

摘要

多巴胺D3受体(D3R)在调节精神运动兴奋剂作用中的潜在作用已引起越来越多的关注。N-[4-[4-(2-甲氧基苯基)-1-哌嗪基]丁基]-2-萘基羧酰胺;又名BP 4.897和DO897)是迄今为止报道的D3R受体最具选择性的部分激动剂之一。BP 897在恒河猴体内支持自我给药(0.3-30 μg/kg),在小鼠体内产生类似可卡因和d -安非他明的区别刺激效应(0.01-17 mg/kg)。在测试的四只猴子中,没有任何一只猴子在超过机动车和生理盐水水平的情况下自行给药BP 897,并且在可卡因或d -安非他明刺激下产生的一般化率低于30%。在服用可卡因或d -安非他明之前服用BP 897,药物杠杆选择的百分比减少。这些结果表明,BP 897具有适合考虑作为可卡因依赖障碍的潜在治疗的活动概况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The D3R partial agonist, BP 897, attenuates the discriminative stimulus effects of cocaine and d -amphetamine and is not self-administered
Growing attention has been directed towards the potential involvement of the dopamine D3 receptor (D3R) in modulating effects of psychomotor stimulants. BP 897 (N-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-2-naphthylcarboxamide; aka BP 4.897 and DO897) is amongst the most selective partial agonists for the D3R receptor thus far reported. BP 897 was tested for its ability to support self-administration in rhesus monkeys (0.3–30 μg/kg) and for its ability to produce cocaine- and d -amphetamine-like discriminative stimulus effects in mice (0.01–17 mg/kg i.p.). BP 897 was not self-administered above vehicle and saline levels in any of the four monkeys tested, and produced less than 30% generalization from either the cocaine or d -amphetamine stimulus. When BP 897 was administered before administrations of cocaine or d -amphetamine, percent drug-lever selections were reduced. These results suggest that BP 897 has a profile of activity suitable for consideration as a potential treatment for cocaine dependency disorders.
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