Comparison of antagonizing potencies of dodecane analogues to isoflurane in goldfish.

摘要

PURPOSE: We reported previously that long-chain fatty acids (carbon atoms > or 12) antagonize volatile anesthetics in goldfish. To examine the contribution of the carboxyl group to the antagonizing potency of fatty acids in vivo, we compared antagonizing potencies to isoflurane in goldfish among terminally substituted dodecane analogues. METHODS: Dodecane (carbon atoms = 12) analogues [fatty acid (DoAC), alcohol (DoAL), alkane (DoAK), sulfate (DoSF), trimethylammonium (DoTA)] were examined. We determined the EC50 (the anesthetic concentration producing a 50% effect) values of isoflurane in the absence or presence of these chemical compounds in goldfish by observing the escape reaction of goldfish from an electrical stimulus. RESULTS: DoAC at higher than 10 microM and DoAL at higher than 20 microM increased the EC50 values of isoflurane in a concentration-dependent manner compared with the control (P < 0.05). DoAC at 50 microM and DoAL at 100 microM increased the EC50 1.7- and 1.6 fold, respectively. DoAK, DoSF, and DoTA showed no significant differences from the control. In the comparison of DoAC and DoAL at the same concentration, DoAC was more effective than DoAL (P < 0.001). CONCLUSION: DoAC and DoAL showed antagonizing potencies to isoflurane, whereas DoAK, DoSF, and DoTA had no effect. DoAC was more effective than DoAL. The findings suggest that polarity of the chemical compounds may be necessary to exert antagonizing potency to isoflurane. Furthermore, a highly negative charge density of the carboxyl group may be responsible for the effective antagonization of DoAC to isoflurane.