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Chemical Compound Review

Ftorotan     2-bromo-2-chloro-1,1,1- trifluoro-ethane

Synonyms: Halotano, Halothan, Narcotan, Narkotan, Alotano, ...
 
 
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Disease relevance of halothane

 

Psychiatry related information on halothane

 

High impact information on halothane

  • In a randomized trial, 30 neonates were assigned to receive deep intraoperative anesthesia with high doses of sufentanil and postoperative infusions of opiates for 24 hours; 15 neonates were assigned to receive lighter anesthesia with halothane and morphine followed postoperatively by intermittent morphine and diazepam [3].
  • In three patients with halothane hepatitis who were studied serially, the lymphocyte abnormality was still present after 13 months [1].
  • In humans, the trait is usually inherited in an autosomal dominant fashion, but in halothane-sensitive pigs with a similar phenotype, inheritance of the disease is autosomal recessive or co-dominant [11].
  • Using a spin-echo pulse sequence it was found that halothane exists in two distinct chemical environments in brain, characterized by different spin-spin relaxation times (T2), chemical shifts and kinetics of occupancy [12].
  • Nematodes bearing the suppressor mutations alone have normal sensitivity to halothane [4].
 

Chemical compound and disease context of halothane

 

Biological context of halothane

 

Anatomical context of halothane

  • Alterations of liver-cell membranes after exposure to halothane [23].
  • In this report, we show for the first time that cultured human skeletal muscle cells derived from MH-susceptible individuals exhibit a half-maximal halothane concentration causing an increase in intracellular Ca2+ concentration which is twofold lower than that of cells derived from MH-negative individuals [24].
  • The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol [25].
  • Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium [26].
  • Similar effects on Ca2+ oscillations and hypercontracture were observed when ryanodine (3 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ release, or cyclopiazonic acid (10 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, were applied instead of halothane [27].
 

Associations of halothane with other chemical compounds

 

Gene context of halothane

  • This investigation tested the hypothesis that cytochrome P450 2E1 (CYP2E1) is responsible for human halothane metabolism in vivo [30].
  • Correlation analysis of the in vitro contracture-test data available for pedigrees bearing these and other RYR1 mutations showed an exceptionally good correlation between caffeine threshold and tension values, whereas no correlation was observed between halothane threshold and tension values [31].
  • Furthermore, high levels of autoantibodies that recognized purified rat CYP2E1 but not purified rat CYP3A were detected by enzyme-linked immunosorbent assay in 14 of 20 (70%) sera from patients with halothane hepatitis [32].
  • The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities [33].
  • Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6) [34].
 

Analytical, diagnostic and therapeutic context of halothane

References

  1. Halothane hepatitis. Detection of a constitutional susceptibility factor. Farrell, G., Prendergast, D., Murray, M. N. Engl. J. Med. (1985) [Pubmed]
  2. Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis. Vergani, D., Mieli-Vergani, G., Alberti, A., Neuberger, J., Eddleston, A.L., Davis, M., Williams, R. N. Engl. J. Med. (1980) [Pubmed]
  3. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. Anand, K.J., Hickey, P.R. N. Engl. J. Med. (1992) [Pubmed]
  4. Genetic analysis of halothane sensitivity in Caenorhabditis elegans. Sedensky, M.M., Meneely, P.M. Science (1987) [Pubmed]
  5. Electrical stimulation of the midbrain mediates metastatic tumor growth. Simon, R.H., Lovett, E.J., Tomaszek, D., Lundy, J. Science (1980) [Pubmed]
  6. Antagonism of the antinocifensive action of halothane by intrathecal administration of GABAA receptor antagonists. Mason, P., Owens, C.A., Hammond, D.L. Anesthesiology (1996) [Pubmed]
  7. Halothane effect on cGMP and control of motor activity in mouse cerebellum. Triner, L., Vulliemoz, Y., Verosky, M., Alpert, M. Anesthesiology (1981) [Pubmed]
  8. Phenylephrine-induced activity in mice as a model of central alpha 1-adrenoceptor function. Effects of acute and repeated administration of antidepressant drugs and electroconvulsive shock. Heal, D.J. Neuropharmacology (1984) [Pubmed]
  9. Pontine cholinergic mechanisms modulate the cortical electroencephalographic spindles of halothane anesthesia. Keifer, J.C., Baghdoyan, H.A., Lydic, R. Anesthesiology (1996) [Pubmed]
  10. Impairment of pulmonary antibacterial defense mechanisms by halothane anesthesia. Manawadu, B.R., LaForce, F.M. Chest (1979) [Pubmed]
  11. Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia. MacLennan, D.H., Duff, C., Zorzato, F., Fujii, J., Phillips, M., Korneluk, R.G., Frodis, W., Britt, B.A., Worton, R.G. Nature (1990) [Pubmed]
  12. Correlation between the anaesthetic effect of halothane and saturable binding in brain. Evers, A.S., Berkowitz, B.A., d'Avignon, D.A. Nature (1987) [Pubmed]
  13. Cardiac arrhythmias in children during outpatient general anaesthesia for dentistry: a prospective randomised trial. Blayney, M.R., Malins, A.F., Cooper, G.M. Lancet (1999) [Pubmed]
  14. Anaesthetic-induced increase in ionised calcium in blood mononuclear cells from malignant hyperthermia patients. Klip, A., Britt, B.A., Elliott, M.E., Pegg, W., Frodis, W., Scott, E. Lancet (1987) [Pubmed]
  15. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Beaune, P., Dansette, P.M., Mansuy, D., Kiffel, L., Finck, M., Amar, C., Leroux, J.P., Homberg, J.C. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  16. Comparison of isoflurane, halothane, and nitrous oxide in status epilepticus. Ropper, A.H., Kofke, W.A., Bromfield, E.B., Kennedy, S.K. Ann. Neurol. (1986) [Pubmed]
  17. Modulation of gap junctional mechanisms during calcium-free induced field burst activity: a possible role for electrotonic coupling in epileptogenesis. Perez-Velazquez, J.L., Valiante, T.A., Carlen, P.L. J. Neurosci. (1994) [Pubmed]
  18. Influence of loading conditions and contractile state on pulmonary venous flow. Validation of Doppler velocimetry. Hoit, B.D., Shao, Y., Gabel, M., Walsh, R.A. Circulation (1992) [Pubmed]
  19. Uncoupling of oxidative phosphorylation in rat liver mitochondria by general anesthetics. Rottenberg, H. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  20. Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans. van Swinderen, B., Shook, D.R., Ebert, R.H., Cherkasova, V.A., Johnson, T.E., Shmookler Reis, R.J., Crowder, C.M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  21. The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Patel, A.B., de Graaf, R.A., Mason, G.F., Rothman, D.L., Shulman, R.G., Behar, K.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  22. L-arginine-induced conducted signals alter upstream arteriolar responsivity to L-arginine. Frame, M.D., Sarelius, I.H. Circ. Res. (1995) [Pubmed]
  23. Alterations of liver-cell membranes after exposure to halothane. Dujovne, C.A. N. Engl. J. Med. (1980) [Pubmed]
  24. Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. Effect Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine receptors. Censier, K., Urwyler, A., Zorzato, F., Treves, S. J. Clin. Invest. (1998) [Pubmed]
  25. Neuronal domains in developing neocortex: mechanisms of coactivation. Yuste, R., Nelson, D.A., Rubin, W.W., Katz, L.C. Neuron (1995) [Pubmed]
  26. Controlled trial of repeated halothane anaesthetics in patients with carcinoma of the uterine cervix treated with radium. Trowell, J., Peto, R., Smith, A.C. Lancet (1975) [Pubmed]
  27. Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture. Siegmund, B., Schlack, W., Ladilov, Y.V., Balser, C., Piper, H.M. Circulation (1997) [Pubmed]
  28. Inhalational anesthetics activate two-pore-domain background K+ channels. Patel, A.J., Honoré, E., Lesage, F., Fink, M., Romey, G., Lazdunski, M. Nat. Neurosci. (1999) [Pubmed]
  29. Selective inhibition of osmotic water flow by general anesthetics to toad urinary bladder. Levine, S.D., Levine, R.D., Worthington, R.E., Hays, R.M. J. Clin. Invest. (1976) [Pubmed]
  30. Identification of the enzyme responsible for oxidative halothane metabolism: implications for prevention of halothane hepatitis. Kharasch, E.D., Hankins, D., Mautz, D., Thummel, K.E. Lancet (1996) [Pubmed]
  31. Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation. Manning, B.M., Quane, K.A., Ording, H., Urwyler, A., Tegazzin, V., Lehane, M., O'Halloran, J., Hartung, E., Giblin, L.M., Lynch, P.J., Vaughan, P., Censier, K., Bendixen, D., Comi, G., Heytens, L., Monsieurs, K., Fagerlund, T., Wolz, W., Heffron, J.J., Muller, C.R., McCarthy, T.V. Am. J. Hum. Genet. (1998) [Pubmed]
  32. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Eliasson, E., Kenna, J.G. Mol. Pharmacol. (1996) [Pubmed]
  33. Goalpha regulates volatile anesthetic action in Caenorhabditis elegans. van Swinderen, B., Metz, L.B., Shebester, L.D., Mendel, J.E., Sternberg, P.W., Crowder, C.M. Genetics (2001) [Pubmed]
  34. Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6). Minoda, Y., Kharasch, E.D. Anesthesiology (2001) [Pubmed]
  35. Hepatic glutathione S-transferase release after halothane anaesthesia: open randomised comparison with isoflurane. Allan, L.G., Hussey, A.J., Howie, J., Beckett, G.J., Smith, A.F., Hayes, J.D., Drummond, G.B. Lancet (1987) [Pubmed]
  36. Halothane shortens acetylcholine receptor channel kinetics without affecting conductance. Lechleiter, J., Gruener, R. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  37. Subcellular distribution of an inhalational anesthetic in situ. Eckenhoff, R.G., Shuman, H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
 
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