Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
Department of General Surgery, Chi-Mei Medical Center, Tainan and Liouying, Taiwan; Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
Eur J Pharmacol. 2019 Mar 5;846:73-78. doi: 10.1016/j.ejphar.2019.01.009. Epub 2019 Jan 11.
The aim of the study was to investigate the analgesic effects of adding serotonin to oxybuprocaine or proxymetacaine preparations. We employed a rat model of the cutaneous trunci muscle reflex (CTMR) to conduct the dose-response curves and duration of drugs (oxybuprocaine, proxymetacaine, or serotonin) as an infiltrative anesthetic. The use of isobolographic methods to analyze the drug-drug interactions. We showed that oxybuprocaine and proxymetacaine, as well as serotonin produced dose-dependent skin antinociception. On the basis of 50% effective dose (ED), the rank order of drug potency was serotonin [7.22 (6.45-8.09) μmol/kg] < oxybuprocaine [1.03 (0.93-1.15) μmol/kg] < proxymetacaine [0.59 (0.53-0.66) μmol/kg] (P < 0.01 for each comparison). The sensory block duration of serotonin was longer (P < 0.01) than that of oxybuprocaine or proxymetacaine at the equipotent doses (ED, ED, and ED). The mixture of serotonin with oxybuprocaine or proxymetacaine produced a better analgesic effect than the drug itself. We have concluded that oxybuprocaine, proxymetacaine, or serotonin displays dose-related cutaneous analgesia. Oxybuprocaine or proxymetacaine is more potent and has a shorter duration of cutaneous analgesia than serotonin. Serotonin produces a synergistic antinociceptive interaction with oxybuprocaine or proxymetacaine.
本研究旨在探讨在氧布比卡因或普罗卡因制剂中加入 5-羟色胺对镇痛效果的影响。我们采用大鼠皮内 Trunci 肌反射（CTMR）模型，绘制了药物（氧布比卡因、普罗卡因或 5-羟色胺）作为浸润性麻醉剂的剂量反应曲线和作用持续时间。采用等辐射分析方法分析药物间的相互作用。结果显示，氧布比卡因、普罗卡因和 5-羟色胺均能产生剂量依赖性的皮肤镇痛作用。根据 50%有效剂量（ED），药物的相对效能顺序为 5-羟色胺[7.22（6.45-8.09）µmol/kg]＜氧布比卡因[1.03（0.93-1.15）µmol/kg]＜普罗卡因[0.59（0.53-0.66）µmol/kg]（每种比较均 P＜0.01）。在等效剂量（ED、ED 和 ED）下，5-羟色胺的感觉阻滞持续时间比氧布比卡因或普罗卡因更长（P＜0.01）。5-羟色胺与氧布比卡因或普罗卡因混合使用产生的镇痛效果优于药物本身。我们的结论是，氧布比卡因、普罗卡因或 5-羟色胺均具有剂量依赖性的皮肤镇痛作用。氧布比卡因或普罗卡因比 5-羟色胺作用更强、作用持续时间更短。5-羟色胺与氧布比卡因或普罗卡因产生协同的镇痛相互作用。
