Shah S, Duttaroy A, Davis T, Yoburn B C
Department of Pharmaceutical Sciences, College of Pharmacy, St. John's University, Queens, NY 11439.
Pharmacol Biochem Behav. 1994 Nov;49(3):773-6. doi: 10.1016/0091-3057(94)90101-5.
The effects of in vivo pertussis toxin (PTX) treatment on the functional effects of opioid agonists were examined in the mouse. Mice were injected intracerebroventricularly (ICV), or intrathecally (IT), or IT and ICV with PTX, and dose-response studies of the antinociceptive action of systemic (SC) morphine, fentanyl, and etorphine were conducted 10 days later. IT PTX decreased the potency (approximately 4.5-fold) of morphine more than ICV administration (approximately 1.5-fold), whereas the combination of IT and ICV administration produced an additive effect. When PTX was administered spinally and supraspinally, the potency of morphine, fentanyl, and etorphine was reduced similarly (approximately 5-7-fold), indicating that the effect of PTX does does not vary considerably among agonists of different intrinsic efficacies. These studies indicate that in vivo PTX can reduce the potency of opioid agonists with different intrinsic efficacies, and that spinal mechanisms appear to be more sensitive to PTX treatment.
在小鼠中研究了体内百日咳毒素（PTX）处理对阿片类激动剂功能效应的影响。给小鼠脑室内（ICV）、鞘内（IT）或同时经IT和ICV注射PTX，10天后进行全身（皮下，SC）注射吗啡、芬太尼和埃托啡镇痛作用的剂量反应研究。与ICV给药（约1.5倍）相比，IT注射PTX使吗啡的效价降低得更多（约4.5倍），而IT和ICV联合给药产生相加效应。当PTX经脊髓和脊髓上给药时，吗啡、芬太尼和埃托啡的效价降低程度相似（约5 - 7倍），表明PTX的作用在不同内在效能的激动剂之间没有显著差异。这些研究表明，体内PTX可降低不同内在效能阿片类激动剂的效价，且脊髓机制似乎对PTX处理更敏感。
