Disease relevance of methoxyflurane

• Body weight gain was lower in both the ether- and Brevital-treated groups as compared to the group anesthetized with methoxyflurane [1].
• Currently used fluorinated anesthetics are chemically related to methoxyflurane (MF), a drug that caused many cases of clinical acute renal failure during previous widespread use [2].
• To investigate the pathogenesis of acute Mycoplasma pneumoniae infection, BALB/c mice were anesthetized with metofane, and M. pneumoniae was introduced intranasally on days 0, 1, and 2 [3].
• The toxicity and safety of methoxyflurane were evaluated [4].
• Helium pressure failed to antagonize the depressant effects of halothane (0.25-0.5 mM) on nicotinic transmission and of halothane or methoxyflurane (0.24 mM) on muscarinic transmission in the ganglion [5].

Psychiatry related information on methoxyflurane

• A similar pattern was observed for increasing concentrations of 1,1,1-trichloroethane and methoxyflurane but changes in open arm activity were only observed at concentrations that increased locomotor activity [6].
• The analgesic effect of subanaesthetic concentrations of ether, trichloroethylene, methoxyflurane and halothane has been investigated previously using either clinical assessment or pain threshold measurements, but with conflicting results [7].
• A comparison of the analgesic effects of methoxyflurane-nitrous oxide and nitrous oxide alone during labour related to the Eysenck personality inventory test [8].

High impact information on methoxyflurane

• Inhalation anesthesia with ether or methoxyflurane was accomplished with a closed recirculatory system that allowed a short induction time for anesthesia and a good control over the concentration of anesthetic [1].
• Survival rates during the 10 weekly instillations were least for the Brevital-treated group and greatest for the methoxyflurane-treated group [1].
• The gerbils were treated with either saline vehicle or 10 mg/kg i.p. of one of the test drugs 30 minutes before and again 2 hours after a 10-minute period of bilateral carotid artery occlusion or sham occlusion under light methoxyflurane anesthesia [9].
• The effects of seven anesthetics (thiopentone, 50 mg/kg ip; pentobarbitone, 50 mg/kg ip; chloral hydrate, 300 mg/kg ip; urethane, 1,5 g/kg, 1/2ip, 1/2sc; ether; methoxyflurane, 1,5%; halothane, 2%) on basal serum TSH concentrations and on the cold-induced as well as the TRH-induced TSH responses were studied in Sprague-Dawley rats [10].
• 2. When ether or methoxyflurane was added to the gas stream that superfused the surface of the preparations, the population e.p.s.p.s. and population spikes were depressed at lower concentrations than those required to depress the compound action potential of the afferent fibres [11].

Chemical compound and disease context of methoxyflurane

• The lack of toxicity of isoflurane is consistent with the results of other reproductive studies in animals that have examined chronic intermittent exposure to subanesthetic concentrations of halothane, enflurane, methoxyflurane, and nitrous oxide [12].
• A study of 405 patients revealed that the substitution of 0.1% trichloroethylene for 0.1% methoxyflurane in a previously established technique of anaesthesia led to no remarkable changes in the incidence of postoperative nausea, vomiting or headache [13].
• The effect of methoxyflurane on the hypoxic pulmonary vasoconstrictor response in the dog lung was assessed by measuring the redistribution of pulmonary blood flow in response to two levels of unilateral alveolar hypoxia [14].
• FD anesthesia was associated with tachycardia and MF anesthesia resulted in hypotension; both showed poor Evans blue staining [15].
• To investigate if glycine toxicity is a mechanism promoting a fatal outcome when the solution is absorbed, we administered glycine 200 or 300 ml kg-1 dissolved in sterile water or normal saline, and also normal saline alone, over 60 min by i.v. infusion to 100 mice under methoxyflurane anaesthesia [16].

Biological context of methoxyflurane

• The action of ether and methoxyflurane on synaptic transmission in isolated preparations of the mammalian cortex [11].
• 1. The actions of ether and methoxyflurane on the evoked potentials of in vitro preparations of the guinea-pig olfactory cortex were studied [11].
• Methoxyflurane biotransformation followed either an unbounded curve with empirical formula y = a ln(bx + 1) or an asymptotic curve with formula (see article) No substrate inhibition was observed [17].
• After recovery from surgery, acute experiments on blood pressure were conducted under methoxyflurane/nitrous oxide anesthesia [18].
• Fluoride in bone of rats anesthetized during gestation with enflurane or methoxyflurane [19].

Anatomical context of methoxyflurane

• However, using hepatic microsomes, sevoflurane and methoxyflurane were defluorinated in vitro at essentially the same rate [20].
• Effects of anesthetics, dibucaine and methoxyflurane on the ATPase activity and physical state of Tetrahymena surface membranes [21].
• Halothane showed a single resonance in erythrocytes and multiple resonances in muscle and nerve, while methoxyflurane showed multiple resonances in both muscle and erythrocytes [22].
• Solubility coefficients for seven inhalation anesthetic agnets were determined in maternal and fetal blood at 37 C. Halothane, isoflurane, diethyl ether, and nitrous oxide were significantly more soluble in maternal than in fetal blood, while methoxyflurane, fluroxene, and cyclopropane were significantly less soluble [23].
• Inhibition by enflurane and methoxyflurane of postdrive hyperpolarization in canine Purkinje fibers [24].

Associations of methoxyflurane with other chemical compounds

• Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia [25].
• Maternal and neonatal plasma inorganic fluoride levels after methoxyflurane analgesia for labor and delivery [26].
• The susceptibility to biotransformation increases in the following order: isoflurane, enflurane, halothane, fluroxene, methoxyflurane [27].
• 5. Although the sample sizes were too small to demonstrate statistical significance, neurons exhibiting a resting discharge were more likely to show a bursting pattern in methoxyflurane-anesthetized preparations than were neurons in pentobarbital sodium-anesthetized preparations [28].
• The discrepancy between defluorination of sevoflurane and methoxyflurane in vivo and in vitro was probably due to differences in tissue solubility between the drugs [20].

Gene context of methoxyflurane

• P450 2E1 is the principal, but not exclusive enzyme responsible for the metabolism of methoxyflurane, which also appears to be catalyzed by P450s 1A2, 2C9/10, and 2D6 [29].
• Obligatory role of cytochrome b5 in the microsomal metabolism of methoxyflurane [30].
• The EC50 concentration for 5-HT decreased from 1.86 +/- 0.02 microM to 1.07 +/- 0.11 microM (means +/- s.e.mean) due to the presence of 1 MAC (270 microM) methoxyflurane [31].
• The mutant proteins have been expressed in Saccharomyces cerevisiae, purified and assayed for their ability to support the cytochrome P450-catalyzed metabolism of the cytochrome b5 requiring substrate methoxyflurane (G. Vergères and L. Waskell, 1992, J. Biol. Chem. 267, 12583-12591) [32].
• The mutant protein receives electrons from NADPH cytochrome P450 reductase and provides the second electron to cytochrome P450 to catalyze the metabolism of methoxyflurane, a substrate which requires cytochrome b5 for its metabolism, at the same rate as the wild type protein [33].

Analytical, diagnostic and therapeutic context of methoxyflurane

• In methoxyflurane-anesthetized rats, intracoerulear microinfusions of acetyicholine (ACh) (200 mM; 90-120 nl) evoked a four- to fivefold increase in LC neuronal discharge, and a transient EEG desynchronization and decrease in mitral cell discharge [34].
• Renal function in newborns and mothers exposed to methoxyflurane analgesia for labor and delivery [35].
• Ultra-long-duration local anesthesia produced by injection of lecithin-coated methoxyflurane microdroplets [4].
• Hepatitis following the use of methoxyflurane in obstetric analgesia [36].
• Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect [4].

References