| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1991: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
Formation of metabolites of halothane under anaerobic or aerobic cobdition by the reaction mixture of liver microsomes and NADPH was examined using rats, guinea pigs or rabbits. 1.Formation of metabolites of halothane, trifluoroacetic acid and anaerobic metabolites, 2-chlor,1,1,1-trifluoroethane and 2-chloro-1,1-difluoroethylene, were inhibited 50% by 4.96mM and 35.3mM paraquat, respectively. Apossoble mechanism was speculated for the inhibitory effects; one is the impaird formation of halothane-cytochrome p450 complex by the addition of paraquat, and the other is the diversion of electron from cytochrome p450 reductase to generate active paraquat radicals. 2.By in vivo treatment, halothane anaerobic dehalogenation was induced by phenobarbital, thiopental, thiamylal, pentobarbital and secobarbital. 3.The reductive metabolism of halothane was reduced by calcium blocking agents, verapamil, diltiazem, nicardipine and nifedipine. NADPH-cytochrome p450 reductase activity in microsomes did not change by the addition of these drugs. 4.The reductive metabolism of halothane was reduced by analgesic or hyponotic agents, fentanyl, morphine, pentazocine, buprenorphine, ketamine, diazepam, chlorpromazine, and hydroxyzine. NADPH-cytochrome p450 reductase activity in microsomes did not change by the addition of these drugs. 5.The reductive metabolism of halothane was enhanced at 0.3% of isoflurane or 0.5-0.8% of sevoflurane. Higher concentration than 1% of these anesthetics, the reductive metabolism of halothane was inhibited. 6.Elevated serum transaminasen (GOT GPT) and TBA reactive substance by in vivo inhaled halothane to guinea pig were inhibited by the adminstration of Vitamin E. 7.The reductive metabolism of halothane was reduced by Gomisi, driedripe fruit of schizandra chinesis Ball which is medical herb. NADPH-cytochrome p450 reductase activity in microsomes did not change by the addition of this drugs.
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