Chen Yu-Wen, Chen Yen-Chia, Lin Ching-Nan, Chu Chin-Chen, Lin Mao-Tsun, Wang Jhi-Joung, Kao Cheng-Hsing
Department of Medical Research, Chi-Mei Medical Centre, Tainan, Taiwan.
Eur J Pharmacol. 2007 Aug 27;569(3):188-93. doi: 10.1016/j.ejphar.2007.05.019. Epub 2007 Jun 5.
Dextromethorphan, an antitussive, has a complex pharmacologic profile and has not been well studied. Our aim was to evaluate whether dextromethorphan and its metabolites, dextrorphan and 3-methoxymorphinan, have a spinal anaesthetic effect. Using a method of spinal blockade in rats, we evaluated the potencies and durations of the effects of dextromethorphan and its metabolites on spinal blockades of motor function and nociception. Bupivacaine was the active control. We found that dextromethorphan and its metabolites produced a dose-related spinal blockade of motor function and nociception. On an ED(50) basis, the ranks of potencies were bupivacaine>dextrorphan>3-methoxymorphinan>dextromethorphan (p<0.05 for the differences). On an equipotent basis, dextrorphan and bupivacaine produced similarly longer nociceptive blockades than did dextromethorphan and 3-methoxymorphinan (p<0.05 for the differences). Co-administration of dextromethorphan or its metabolites with bupivacaine produced an additive effect. In conclusion, intrathecal injections of dextromethorphan or its metabolites, dextrorphan and 3-methoxymorphinan, produced dose-related spinal blockades of motor function and nociception. The suitability of these drugs as clinical spinal anaesthetics is worth further evaluation.
右美沙芬是一种镇咳药，其药理特性复杂，尚未得到充分研究。我们的目的是评估右美沙芬及其代谢产物右啡烷和3-甲氧基吗啡烷是否具有脊髓麻醉作用。我们采用大鼠脊髓阻滞方法，评估右美沙芬及其代谢产物对运动功能和痛觉脊髓阻滞作用的效能和持续时间。布比卡因作为阳性对照。我们发现右美沙芬及其代谢产物可产生与剂量相关的运动功能和痛觉脊髓阻滞。以半数有效剂量（ED50）为基础，效能排序为布比卡因>右啡烷>3-甲氧基吗啡烷>右美沙芬（差异p<0.05）。在等效剂量基础上，右啡烷和布比卡因产生的痛觉阻滞时间比右美沙芬和3-甲氧基吗啡烷更长（差异p<0.05）。右美沙芬或其代谢产物与布比卡因联合给药产生相加作用。总之，鞘内注射右美沙芬或其代谢产物右啡烷和3-甲氧基吗啡烷可产生与剂量相关的运动功能和痛觉脊髓阻滞。这些药物作为临床脊髓麻醉剂的适用性值得进一步评估。
