The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Alfaxalona     (3R,5S,8S,9S,10S,13S,14S,17S)- 17-ethanoyl...

Synonyms: Alfaxalone, alfaxolone, Alfaxalonum, Alphaxalone, SureCN57756, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Alphaxalone


Psychiatry related information on Alphaxalone


High impact information on Alphaxalone

  • Sex difference in response to alphaxalone anaesthesia may be oestrogen dependent [10].
  • These results, taken together with those of Richards and Hesketh, suggest that the effect of alphaxalone may be mediated by interactions with synaptic membranes that are more specific than simply a generalized change in membrane structure, and that these interactions are affected by sex steroids [10].
  • T-type Ca(2+) channels are believed to play an important role in pain perception, and anesthetic steroids such as alphaxalone and allopregnanolone, which have a 5alpha-configuration at the steroid A, B ring fusion, are known to inhibit T-type Ca(2+) channels and cause analgesia in a thermal nociceptive model (Soc Neurosci Abstr 29:657.9, 2003) [11].
  • To determine whether receptor modulation by intravenous general anesthetics also was affected by these point mutations, we examined the effects of propofol, etomidate, the barbiturate methohexital, and the steroid alphaxalone on wild-type and mutant GABAA receptors expressed in human embryonic kidney 293 cells [12].
  • These results further demonstrate that the actions of general anesthetics at GABA(A) receptors are influenced by receptor subunit composition, and they suggest that the effects of alphaxalone and etomidate are mediated by different binding sites on the receptor complex [13].

Chemical compound and disease context of Alphaxalone


Biological context of Alphaxalone

  • 2. The animals were anaesthetized with sodium pentobarbitone which, as assessed by the effects on the circadian rhythm of plasma ACTH and corticosterone, appeared to be a better anaesthetic than either urethane or alphaxalone for studies on the hypothalamic-pituitary-adrenal system [15].
  • 3. The kinetics of the Na current were not modified by alphaxalone but, in the presence of the drug, the K current showed an apparent fast inactivation [16].
  • However, higher concentrations of alphaxalone (10-100 microM) reversibly suppressed ACh-evoked currents, the IC50 for blockade being 20 microM [17].
  • Protein kinase A inhibition significantly reduced alphaxalone auto-modulation at alpha1beta3gamma2L, alpha6beta3gamma2L, and alpha6beta3delta subtypes while it enhanced potentiation at alpha1beta3delta isoforms suggesting a crucial influence of receptor subunit composition and phosphorylation for steroid actions [18].
  • Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia [19].

Anatomical context of Alphaxalone

  • Geometric requirements for membrane perturbation and anesthetic activity. Conformational analysis of alphaxalone and delta 16-alphaxalone and 2H NMR studies on their interactions with model membranes [20].
  • The ability of volatile (halothane and isoflurane) and nonvolatile (alphaxalone and pentobarbital) general anesthetics to modulate radioligand binding to gamma-aminobutyric acid (GABA)A receptors was examined in an immortalized cell line (WSS-1) expressing rat alpha 1 and gamma 2 subunits [21].
  • The effect of the general anesthetic propofol on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to unwashed membrane preparations from rat cerebral cortex was studied and compared to that of other general anesthetics (pentobarbital, alphaxalone) which are known to enhance GABAergic transmission [22].
  • These effects on the inhibitory Cl(-)-conductance mechanism may be partly responsible for the depressant actions of alphaxalone on the mammalian central nervous system [23].
  • The modulation of the gamma-aminobutyric acidA (GABAA) receptor by alphaxalone has been investigated by use of voltage-clamp recordings from enzymatically isolated bovine chromaffin cells maintained in cell culture [17].

Associations of Alphaxalone with other chemical compounds


Gene context of Alphaxalone

  • However, although maximal current activation by alphaxalone varied only slightly with the specific beta subunit isoform present, the efficacy of etomidate showed a rank order of beta3 > beta2 >>> beta1 [13].
  • Alphaxalone (ALX) does not reduce CRF-potentiated startle by producing a generalized reduction in reactivity, since blockade of CRF-stimulated startle was not accompanied by an ALX-induced reduction in baseline startle amplitude and ALX does not reduce strychnine-potentiated startle [8].
  • 4. At 10 microM, the steroids 5 alpha-pregnan-3 alpha-ol-20-one and alphaxalone (5 alpha-pregnan-3 alpha-ol-11,20-dione), potentiated submaximal GABA responses [29].
  • Alphaxalone, a neurosteroid anesthetic, inhibits norepinephrine transporter function in cultured bovine adrenal medullary cells [30].
  • The potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital [31].

Analytical, diagnostic and therapeutic context of Alphaxalone


  1. Alphaxalone activates a Cl- conductance independent of GABAA receptors in cultured embryonic human dorsal root ganglion neurons. Valeyev, A.Y., Hackman, J.C., Holohean, A.M., Wood, P.M., Katz, J.L., Davidoff, R.A. J. Neurophysiol. (1999) [Pubmed]
  2. Alphaxalone infusion during cardiopulmonary bypass. Coniam, S.W. Anaesthesia. (1980) [Pubmed]
  3. Metabolism of 14C-labelled alphaxalone in man. Strunin, L., Strunin, J.M., Knights, K.M., Ward, M.E. British journal of anaesthesia. (1977) [Pubmed]
  4. Neuroactive steroids exacerbate gamma-hydroxybutyric acid-induced absence seizures in rats. Banerjee, P.K., Snead, O.C. Eur. J. Pharmacol. (1998) [Pubmed]
  5. Etomidate in electroconvulsive therapy. A within-patient comparison with alphaxalone/alphadalone. O'Carroll, T.M., Blogg, C.E., Hoinville, E.A., Savege, T.M. Anaesthesia. (1977) [Pubmed]
  6. Anti-stress action of a corticotropin-releasing factor antagonist on behavioral reactivity to stressors of varying type and intensity. Heinrichs, S.C., Menzaghi, F., Pich, E.M., Baldwin, H.A., Rassnick, S., Britton, K.T., Koob, G.F. Neuropsychopharmacology (1994) [Pubmed]
  7. Anxiolytic activity of steroid anesthetic alphaxalone. Britton, K.T., Page, M., Baldwin, H., Koob, G.F. J. Pharmacol. Exp. Ther. (1991) [Pubmed]
  8. Alphaxalone, a steroid anesthetic, inhibits the startle-enhancing effects of corticotropin releasing factor, but not strychnine. Swerdlow, N.R., Britton, K.T. Psychopharmacology (Berl.) (1994) [Pubmed]
  9. Interaction of the neurosteroid alphaxalone with conventional antiepileptic drugs in different types of experimental seizures. Borowicz, K.K., Zadrozniak, M., Swiader, M., Kowalska, A., Kleinrok, Z., Czuczwar, S.J. Eur. J. Pharmacol. (2002) [Pubmed]
  10. Sex difference in response to alphaxalone anaesthesia may be oestrogen dependent. Fink, G., Sarkar, D.K., Dow, R.C., Dick, H., Borthwick, N., Malnick, S., Twine, M. Nature (1982) [Pubmed]
  11. 5beta-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2+ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo. Todorovic, S.M., Pathirathna, S., Brimelow, B.C., Jagodic, M.M., Ko, S.H., Jiang, X., Nilsson, K.R., Zorumski, C.F., Covey, D.F., Jevtovic-Todorovic, V. Mol. Pharmacol. (2004) [Pubmed]
  12. Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. Krasowski, M.D., Koltchine, V.V., Rick, C.E., Ye, Q., Finn, S.E., Harrison, N.L. Mol. Pharmacol. (1998) [Pubmed]
  13. Differential subunit dependence of the actions of the general anesthetics alphaxalone and etomidate at gamma-aminobutyric acid type A receptors expressed in Xenopus laevis oocytes. Sanna, E., Murgia, A., Casula, A., Biggio, G. Mol. Pharmacol. (1997) [Pubmed]
  14. Incorporation of alphaxalone into different types of liposomes. Dean, T.P., Hider, R.C. J. Pharm. Pharmacol. (1993) [Pubmed]
  15. Effects of adrenalectomy and glucocorticoids on the peptides CRF-41, AVP and oxytocin in rat hypophysial portal blood. Fink, G., Robinson, I.C., Tannahill, L.A. J. Physiol. (Lond.) (1988) [Pubmed]
  16. Interactions between molecules of a steroid anaesthetic (alphaxalone) and ionic channels of nodal membrane in voltage-clamped myelinated nerve fibre. Benoit, E., Carratù, M.R., Mitolo-Chieppa, D. Br. J. Pharmacol. (1988) [Pubmed]
  17. Modulation of GABAA receptor activity by alphaxalone. Cottrell, G.A., Lambert, J.J., Peters, J.A. Br. J. Pharmacol. (1987) [Pubmed]
  18. Auto-modulation of neuroactive steroids on GABA(A) receptors: A novel pharmacological effect. Wegner, F., Rassler, C., Allgaier, C., Strecker, K., Wohlfarth, K. Neuropharmacology (2007) [Pubmed]
  19. Pressure reversal of alphaxalone/alphadolone and methohexitone in tadpoles: evidence for different molecular sites for general anaesthesia. Halsey, M.J., Wardley-Smith, B., Wood, S. Br. J. Pharmacol. (1986) [Pubmed]
  20. Geometric requirements for membrane perturbation and anesthetic activity. Conformational analysis of alphaxalone and delta 16-alphaxalone and 2H NMR studies on their interactions with model membranes. Fesik, S.W., Makriyannis, A. Mol. Pharmacol. (1985) [Pubmed]
  21. Different subunit requirements for volatile and nonvolatile anesthetics at gamma-aminobutyric acid type A receptors. Harris, B.D., Wong, G., Moody, E.J., Skolnick, P. Mol. Pharmacol. (1995) [Pubmed]
  22. The general anesthetic propofol enhances the function of gamma-aminobutyric acid-coupled chloride channel in the rat cerebral cortex. Concas, A., Santoro, G., Mascia, M.P., Serra, M., Sanna, E., Biggio, G. J. Neurochem. (1990) [Pubmed]
  23. Potentiation of gamma-aminobutyric-acid-activated chloride conductance by a steroid anaesthetic in cultured rat spinal neurones. Barker, J.L., Harrison, N.L., Lange, G.D., Owen, D.G. J. Physiol. (Lond.) (1987) [Pubmed]
  24. Rat beta 3 subunits expressed in human embryonic kidney 293 cells form high affinity [35S]t-butylbicyclophosphorothionate binding sites modulated by several allosteric ligands of gamma-aminobutyric acid type A receptors. Slany, A., Zezula, J., Tretter, V., Sieghart, W. Mol. Pharmacol. (1995) [Pubmed]
  25. Prenatal ethanol exposure alters the modulation of the gamma-aminobutyric acidA1 receptor-gated chloride ion channel in adult rat offspring. Allan, A.M., Wu, H., Paxton, L.L., Savage, D.D. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  26. Anaesthetics depress the sensitivity of cortical neurones to L-glutamate. Richards, C.D., Smaje, J.C. Br. J. Pharmacol. (1976) [Pubmed]
  27. Inhibition by anaesthetics of 14C-guanidinium flux through the voltage-gated sodium channel and the cation channel of the 5-HT3 receptor of N1E-115 neuroblastoma cells. Barann, M., Göthert, M., Fink, K., Bönisch, H. Naunyn Schmiedebergs Arch. Pharmacol. (1993) [Pubmed]
  28. Structure-selective anesthetic action of steroids: anesthetic potency and effects on lipid and protein. Ueda, I., Tatara, T., Chiou, J.S., Krishna, P.R., Kamaya, H. Anesth. Analg. (1994) [Pubmed]
  29. Allosteric modulation of an expressed homo-oligomeric GABA-gated chloride channel of Drosophila melanogaster. Hosie, A.M., Sattelle, D.B. Br. J. Pharmacol. (1996) [Pubmed]
  30. Alphaxalone, a neurosteroid anesthetic, inhibits norepinephrine transporter function in cultured bovine adrenal medullary cells. Horishita, T., Minami, K., Yanagihara, N., Shiraishi, M., Okamoto, T., Shiga, Y., Ueno, S., Shigematsu, A. Anesth. Analg. (2002) [Pubmed]
  31. Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a novel positive modulator of GABAA receptors. Mascia, M.P., Asproni, B., Busonero, F., Talani, G., Maciocco, E., Pau, A., Cerri, R., Sanna, E., Biggio, G. Eur. J. Pharmacol. (2005) [Pubmed]
  32. Mechanism-based modeling of the pharmacodynamic interaction of alphaxalone and midazolam in rats. Visser, S.A., Huntjens, D.R., van der Graaf, P.H., Peletier, L.A., Danhof, M. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  33. Proceedings: The determination of alphaxalone in human blood by gas-liquid chromatography. Dubois, M., Allison, J., Geddes, I.C. British journal of anaesthesia. (1975) [Pubmed]
  34. Pharmacokinetics of althesin--comparison with lignocaine. Simpson, M.E. British journal of anaesthesia. (1978) [Pubmed]
WikiGenes - Universities