GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats
GluN2A-selective positive allosteric modulator-nalmefene-flumazenil reverses ketamine-fentanyl-dexmedetomidine-induced anesthesia and analgesia in rats
复制标题
GluN2A选择性正变构调节剂纳美芬-氟马西尼逆转氯胺酮-芬太尼-右美托咪定诱导的大鼠麻醉和镇痛
DOI：
10.1038/s41598-020-62192-8
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发表时间：
2020-03-24
影响因子：
4.6
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
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作者：
Li, Chunzhu;Yan, Jia;Jiang, Hong
麻醉剂用于在手术过程中产生催眠和镇痛作用，但手术后长时间麻醉不利于动物或患者的恢复。因此，找到适当的治疗方法来对抗麻醉剂的影响可以促进术后恢复。在目前的研究中，我们发现了一种GluN 2A选择性正变构调节剂（PAM）在氯胺酮诱导的麻醉中的新作用，并研究了PAM与纳美芬和氟马西尼（PNF）联合在逆转麻醉剂组合（氯胺酮-芬太尼-右美托咪定，KFD）作用中的作用。PAM处理剂量依赖性地减少氯胺酮诱导的翻正反射丧失（LORR）的持续时间。与KFD组相比，KFD + PNF组LORR持续时间和镇痛效果明显缩短。同时，连续给予PNF和KFD对心血管和呼吸系统无不良影响。KFD组和KFD + PNF组大鼠的肝肾功能和认知功能均无变化。KFD + PNF组运动协调功能恢复快于KFD组。总之，我们的研究结果表明PNF组合作为麻醉拮抗治疗策略的潜在应用。
Anesthetics are used to produce hypnosis and analgesic effects during surgery, but anesthesia for a long time after the operation is not conducive to the recovery of animals or patients. Therefore, finding appropriate treatments to counter the effects of anesthetics could enhance postoperative recovery. In the current study, we discovered the novel role of a GluN2A-selective positive allosteric modulator (PAM) in ketamine-induced anesthesia and investigated the effects of the PAM combined with nalmefene and flumazenil (PNF) in reversing the actions of an anesthetic combination (ketamine-fentanyl-dexmedetomidine, KFD). PAM treatment dose-dependently decreased the duration of the ketamine-induced loss of righting reflex (LORR). Compared with those in the KFD group, the duration of LORR and the analgesic effect of the KFD + PNF group were obviously decreased. Meanwhile, successive administration of PNF and KFD had no adverse effects on the cardiovascular and respiratory systems. Both the KFD group and the KFD + PNF group showed no changes in hepatic and renal function or cognitive function in rats. Moreover, the recovery of motor coordination of the KFD + PNF group was faster than that of the KFD group. In summary, our results suggest the potential application of the PNF combination as an antagonistic treatment strategy for anesthesia.