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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2002, Vol. 7 ›› Issue (1): 5-8.

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Combined inhibitory effects of propofol and midazolam on macroscopic sodium currents in rat sympathetic ganglion neurons

ZHENG Ji-Jian, ZHUANG Xin-Liang, DU Dong-Ping, MAO Qing-Hong, XU Guo-Hui   

  1. Department of Anesthesiology, Shanghai First People's Hospital, Shanghai 200080
  • Received:2001-09-10 Revised:2001-10-12 Online:2002-02-26 Published:2020-11-27

Abstract: AIM: To study the interactions of propo-fol and midazolam on the whole-cell sodium channel cur-rents in rat sympathetic ganglion neurons.METHODS: Whole-cell patch-clamp recordings were made from enzy-matically isolated rat (7-10 d)superior cervical sympa-thetic ganglion neurons.Isobolographic analysis was ap-plied to evaluate the potency of combinations of propofol and midazolam on Na+channel currents.RESULTS: Under Vh = 80 mV and Vt =0 mV. Propofol and mida-zolam dose-dependently blocked Na+ currents with a mean drug concentration required to produce 50%current inhibition(IC50 ):33.12 μmol·L-1 and18.35 μmol·L-1; clinically relevant concentrations of propofol and midazo-lam reduced Na+ peak currents by 27.66%(P <0.01) and 19.88%(P <0.05).The IC50 values of midazolam combined with 1/4 and 3/4 IC50 propofol located in the 95% confidence limits of theoretical additive line; the IC50 values of midazolam combined with 1/2 IC50 propofol located under the 95%confidence limitsof theoretical ad-ditive line. CONCLUSION: Clinically relevant concen-trations of propofol and midazolam have direct and dose-dependent inhibition on the Na+ channel currents of rat sympathetic ganglion neurons.The interactions between propofol and midazolam at Na+ channel current are addi-tive, in addition to the synergism which equi-effective doses are used.Reduction of cardiovascular depression during co-inductionof propofol and midazolam may be rel-evant to the reduction of doses.

Key words: anesthesia, propofol, midazolam, sym-pathetic ganglion, patch-clamp/sodium channel, drng in-teraction

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