A new formulation of dezocine, Cyc-dezocine, reduces oxycodone self-administration in female and male rats.
A new formulation of dezocine, Cyc-dezocine, reduces oxycodone self-administration in female and male rats.
复制标题
地佐辛的新配方 Cyc-dezocine 可减少雌性和雄性大鼠的羟考酮自我给药。
DOI：
10.1016/j.neulet.2023.137479
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发表时间：
2023
影响因子：
2.5
通讯作者：
Barr,GordonA
中科院分区：
文献类型：
--
作者：
Schmidt,HeathD;Zhang,Yafang;Xi,Jin;Zanni,Giulia;Liu,Renyu;Barr,GordonA
地佐辛是一种部分μ阿片受体激动剂，此前在美国用作围手术期急性疼痛的镇痛药，现在是中国使用最多的围手术期镇痛药。一般而言，曲马多辛耐受性良好，致死性呼吸抑制的风险相对较低。据我们所知，没有关于西兰花碱成瘾的报告，这表明西兰花碱的滥用倾向较低。本研究的总体目标是确定开发用于腹膜内或鼻内给药的新的阿托西汀制剂（环阿托西汀）减少大鼠自愿阿片类药物摄入的疗效。一组雄性大鼠按照固定比例5强化方案静脉内自我给予羟考酮。一旦羟考酮服用稳定，对大鼠全身注射溶剂或环地佐辛进行预处理。环丙沙星剂量依赖性地减少静脉内羟考酮自我给药。第二组雄性和雌性大鼠从饮用水中自我口服羟考酮。一旦羟考酮服用稳定，则用鼻内环丙沙星对大鼠进行预处理。与我们的静脉内羟考酮研究中腹膜内环丙沙星的作用一致，鼻内环丙沙星减弱了口服羟考酮自我给药。总之，这些发现支持需要进一步研究环辛二烯用于治疗阿片类药物使用障碍的治疗潜力。
Dezocine is a partial mu opioid receptor agonist previously used as an analgesic for perioperative acute pain in the US and is now the most used perioperative analgesic in China. In general, dezocine is well-tolerated, with relatively minimal risk of fatal respiratory depression. To our knowledge, there are no reports of dezocine addiction, which suggests that the abuse liability of dezocine is low. The overarching goal of this study was to determine the efficacy of a novel formulation of dezocine (Cyc-dezocine), developed for intraperitoneal or intranasal administration, to reduce voluntary opioid taking in rats. One cohort of male rats self-administered intravenous oxycodone on a fixed-ratio 5 schedule of reinforcement. Once oxycodone taking stabilized, rats were pretreated with systemic injections of vehicle or Cyc-dezocine. Cyc-dezocine dose-dependently reduced intravenous oxycodone self-administration. A second cohort of male and female rats self-administered oral oxycodone from drinking water. Once oxycodone taking stabilized, rats were pretreated with intra-nasal Cyc-dezocine. Consistent with the effects of i.p. Cyc-dezocine in our intravenous oxycodone studies, intra-nasal Cyc-dezocine attenuated oral oxycodone self-administration. Together, these findings support the need for further studies investigating the therapeutic potential of Cyc-dezocine for treating opioid use disorder.