Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys
Clocinnamox antagonism of opioid suppression of schedule-controlled responding in rhesus monkeys
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DOI：
10.1007/bf02246641
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发表时间：
1996-02-01
影响因子：
3.4
通讯作者：
Woods, JH
中科院分区：
文献类型：
--
作者：
Butelman, ER;Negus, SS;Woods, JH
在恒河猴（n=3-4）中，研究了clocinnamox对阿片类激动剂的拮抗作用，这些阿片类激动剂作用于mu， kappa和部分衍生物受体，在固定比例30 （FR 30）的食物递送计划下反应。Clocinnamox （0.032-0.1 mg/kg）在预处理3小时或1天后呈剂量依赖性拮抗芬太尼（0.001-0.32 mg/kg）；服用氯硝莫后1周，激动剂的效力明显恢复。依替硝嗪（0.0001 ~ 0.01 mg/kg）也被氯西那莫克斯（0.1 mg/kg）拮抗，但拮抗程度低于芬太尼。较小程度的拮抗作用不是由于埃托硝泽烯出现非阿片类药物反应的减少作用，因为竞争性拮抗剂quadazocine （0.1 mg/kg）在clolocinnamox （0.1 mg/kg）存在下使埃托硝泽烯的剂量-效应曲线发生偏移。Clocinnamox （0.1-0.32 mg/kg）不能拮抗部分衍生物激动剂BW373U86 （0.0.01-1.0 mg/kg）或kappa激动剂U69,593 （0.001-0.032 mg/kg）的速率抑制作用。这些结果与先前的体内和体外证据一致，这些证据表明cllocinnamox是一种不可克服的拮抗剂，对mu- over kappa-和delta受体具有选择性。
The antagonist effects of clocinnamox were evaluated against opioid agonists, acting at mu, kappa and partial derivative-receptors, in rhesus monkeys (n=3-4) responding under a fixed-ratio 30 (FR 30) schedule for food delivery. Clocinnamox (0.032-0.1 mg/kg) dose-dependently antagonized fentanyl (0.001-0.32 mg/kg) after either a 3-h or 1-day pretreatment; there was substantial recovery of agonist potency by 1 week after clocinnamox. Etonitazene (0.0001-0.01 mg/kg) was also antagonized by clocinnamox (0.1 mg/kg), but to a lesser extent than fentanyl. The smaller extent of antagonism was not due to the appearance of non mu-opioid response-decreasing effects of etonitazene, since the competitive antagonist quadazocine (0.1 mg/kg) shifted the etonitazene dose-effect curve in the presence of clocinnamox (0.1 mg/kg). Clocinnamox (0.1-0.32 mg/kg) did not antagonize the rate-suppressing effects of the partial derivative-agonist BW373U86 (0.0.01-1.0 mg/kg) or the kappa-agonist U69,593 (0.001-0.032 mg/kg). These results are consistent with previous in vivo and in vitro evidence that characterized clocinnamox as an insurmountable antagonist, with selectivity for mu- over kappa- and delta-receptors.