Department of Anesthesiology, Chi Mei Medical Center, Yong Kang, Tainan, 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.
Pharmacol Rep. 2017 Oct;69(5):846-850. doi: 10.1016/j.pharep.2017.03.017. Epub 2017 Mar 29.
The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception.
The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug-drug interactions were evaluated by isobologram.
Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED]), the relative potency was bupivacaine (0.43 [0.37-0.50] μmol)>serotonin (1.27 [1.15-1.40] μmol) (p<0.01). At the equi-anesthetic doses (ED, ED and ED), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception.
The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine+serotonin than bupivacaine alone.
本实验旨在研究长效局部麻醉药布比卡因与 5-羟色胺联合应用诱导皮肤镇痛的效果。
评估皮肤镇痛，表现为大鼠背部皮肤刺痛后竖毛肌反射（CTMR）抑制。以剂量依赖的方式构建布比卡因、5-羟色胺单独以及布比卡因与 5-羟色胺共同注射的皮肤镇痛作用，并用等辐射图评估药物相互作用。
皮下 5-羟色胺和局部麻醉药布比卡因均引起剂量相关的皮肤镇痛。在等效基础上（50%有效剂量[ED]），相对效力为布比卡因（0.43[0.37-0.50]μmol）>5-羟色胺（1.27[1.15-1.40]μmol）（p<0.01）。在等麻醉剂量（ED、ED 和 ED）下，布比卡因的持续时间与 5-羟色胺产生皮肤镇痛作用的持续时间相似。布比卡因和 5-羟色胺联合给药显示出协同镇痛作用。
临床前数据表明，与布比卡因相比，5-羟色胺在诱导皮肤镇痛作用方面效力较低，但作用持续时间相似。我们还发现，与单独使用布比卡因相比，布比卡因+5-羟色胺可产生更深的感觉阻滞。
