Department of Physical Therapy, China Medical University, Taichung, Taiwan.
Eur J Pharmacol. 2012 Jan 30;675(1-3):22-5. doi: 10.1016/j.ejphar.2011.11.042. Epub 2011 Dec 7.
The aim of this study was to evaluate the local anesthetic effect of nisoxetine as infiltrative cutaneous analgesic. After rats were injected subcutaneously with nisoxetine, dose-response curves were constructed. The cutaneous anesthetic effect of nisoxetine or MK-801 (dizocilpine) was compared with lidocaine, a traditional local anesthetic. We found that nisoxetine and MK-801 acted like lidocaine and elicited dose-related cutaneous (local) anesthesia. The relative potency was nisoxetine>MK-801>lidocaine (P<0.01) as infiltrative anesthesia of skin. On an equianesthetic doses (20% effective dose [ED₂₀], ED₅₀, and ED₈₀), nisoxetine produced longer action of cutaneous anesthesia than that of lidocaine or MK-801 (P<0.01). Coadministration of nisoxetine or lidocaine with MK-801 showed an additive cutaneous anesthesia. Neither local injection of a large dose of nisoxetine, MK-801 nor lidocaine in the thigh area produced cutaneous anesthesia (data not shown). In conclusion, nisoxetine had a local anesthetic effect as infiltrative cutaneous analgesia with durations of actions longer than that of lidocaine or MK-801. That N-methyl-d-aspartate receptors may not contribute to the cutaneous (local) anesthetic effect of nisoxetine or lidocaine.
本研究旨在评估奈索西汀作为浸润性皮肤镇痛剂的局部麻醉效果。在大鼠皮下注射奈索西汀后，构建剂量-反应曲线。将奈索西汀或 MK-801（地卓西平）的皮肤麻醉效果与传统局部麻醉药利多卡因进行比较。我们发现，奈索西汀和 MK-801 与利多卡因作用相似，引发剂量相关的皮肤（局部）麻醉。作为皮肤浸润麻醉，相对效力为奈索西汀>MK-801>利多卡因（P<0.01）。在等麻醉剂量（20%有效剂量[ED₂₅]、ED₅₀和 ED₈₀）下，奈索西汀产生的皮肤麻醉作用比利多卡因或 MK-801 长（P<0.01）。奈索西汀或利多卡因与 MK-801 联合给药显示出相加的皮肤麻醉作用。大腿区域局部注射大剂量的奈索西汀、MK-801 或利多卡因均未产生皮肤麻醉作用（未显示数据）。总之，奈索西汀具有局部麻醉作用，作为浸润性皮肤镇痛剂，作用持续时间长于利多卡因或 MK-801。N-甲基-D-天冬氨酸受体可能不会影响奈索西汀或利多卡因的皮肤（局部）麻醉作用。
