Lidocaine may contribute to general anesthesia by different mechanisms in mammalian central nervous system

نویسندگان

  • Mingyang Shi
  • Guangbo Xie
  • Xiaoshuai Fan
  • Weidong Pan
  • Xiaoshuang Zhou
  • Jingbo Yuan
  • Zeyi Chen
  • Guo Chen
چکیده

Background: Systemic administration of local anesthetics can produce systemic actions, but the details of these actions and mechanisms are still unclear. We evaluated the systemic actions of three local anesthetics and their underlying mechanisms in this study. Methods: Lidocaine, bupivacaine and ropivacaine were injected into C57BL/6 mice through tail vein, alone or together with hyperpolarization-activated cyclic nucleotide-gated (HCN) channels blocker ZD 7288 or N-methyl-D-aspartic acid (NMDA) receptor blocker MK-801, and hypnotic actions of these local anesthetics, were evaluated by the length of loss of righting reflex (LORR). Results: All of these three local anesthetics directly produced hypnotic actions with half effective dose (ED50) of 19.0±2.4, 4.3±0.2 and 4.2±0.4 mg/kg. The effects of lidocaine on LORR were enhanced by ZD 7288, ED50 from 19.0±2.4 mg/kg to 14.1±1.0 mg/ kg (P<0.01) or to 13.1±0.8 mg/kg (P<0.01) by MK-801, respectively. The effects of ropivacaine on LORR were weakened by ZD 7288 or MK-801, with ED50 from 4.2±0.4 mg/kg to 6.9±0.3 mg/kg (P<0.01) or to 6.7±0.2 mg/ kg (P<0.01). ZD 7288 could weaken the effects of bupivacaine on LORR with ED50 from 4.3±0.2 mg/kg to 5.6±0.4 mg/kg (P<0.01), while MK-801 had no influence on it with ED50 from 4.3±0.2 mg/kg to 4.5±0.5 mg/kg (P>0.05). Conclusion: HCN channels and NMDA receptor may play an important role in the systemic actions of local anesthetics. The mechanisms of effects of lidocaine on the mammalian central nervous system may be different from those of bupivacaine and ropivacaine.

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تاریخ انتشار 2017