In vivo pharmacological resultant analysis reveals noncompetitive interactions between opioid antagonists in the rat tail-withdrawal assay.
In vivo pharmacological resultant analysis reveals noncompetitive interactions between opioid antagonists in the rat tail-withdrawal assay.
复制标题
体内药理学结果分析揭示了大鼠尾部戒断试验中阿片类拮抗剂之间的非竞争性相互作用。
DOI：
10.1038/sj.bjp.0706946
复制
发表时间：
2006
影响因子：
7.3
通讯作者：
Walker,EA
中科院分区：
文献类型：
--
作者：
Walker,EA
Background and purposePharmacological resultant analysis is a technique that can detect secondary effects of competitive antagonistsin vitro. The utility of pharmacological resultant analysis as a potential tool for the investigation of antagonist interactionsin vivowas examined in the present study using two opioid antagonists, naltrexone and CTAP.Experimental approachUsing the experimental design of pharmacological resultant analysis, the well‐characterized opioid antagonist naltrexone was examined in the presence of multiple doses of CTAP to block the antinociceptive effects of morphine in the rat warm‐water (55oC), tail‐withdrawal assay.Key resultsAlone, all doses of naltrexone, CTAP, and CTOP examined blocked the antinociceptive effects of morphine. In the presence of fixed doses of 1 or 10 μg CTAP, increasing doses of naltrexone produced dose‐dependent shifts to the right in the morphine dose‐response curve. However, a lower dose of naltrexone in combination with 1 or 10 μg CTAP failed to alter the morphine dose‐response curve. In the presence of a fixed dose of 0.1 mg kg−1naltrexone, CTAP doses produced irregular shifts to the right in the morphine dose‐response curves.Conclusions and implicationsResultant analysis was applied and an apparent pKCvalue for CTAP was found to be one log unit higher than the apparent pA2value for CTAP, evidence that CTAP may have secondary actions or that a signal transducer function may be altered by the combinations of these antagonists. Taken together, these data suggest pharmacological resultant analysis can reveal novel interactions between antagonistsin vivo.British Journal of Pharmacology(2006)149, 1071–1082. doi:10.1038/sj.bjp.0706946
