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23h, 11h2, 3h3, t13, 1cc, 34c, smiles, interactive, image, model, jsmol, mol, 332, 484, molar, mass, formula, physical, 100, dtxsid9022576, epa, comptox, dashboard, chembl190279, chembl, d07282, kegg, bd07m97b2a, unii, 94637, chemspider, db11371, drugbank, 5461, iuphar, bps, 104845, cid, pubchem, 23930, cas, acetyl, dimethyl, tetradecahydrocyclopenta, phenanthren, iupac, identifiers, renal, excretion, hepatic, protein, veterinarian, schedule, prescription, qn01ax05, atcvet, class, ahfs, trade, pharmaceutical, discuss, appropriate, relies, too, heavily, primary, verification, adding, meet, problem, contains, structured, inconsistent, tone, unclear, encyclopedic, statements, several, claims, weakly, appears, anecdotal, overly, detailed, entry, quality, standards, require, messages, free, item, projects, printable, version, download, print, export, switch, legacy, parser, get, shortened, url, information, permanent, what, english, српски, srpski, srpskohrvatski, српскохрватски, português, 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methyl 1 2 3 4 5 6 7 8 9 12 14 15 16 17 tetradecahydrocyclopenta a phenanthren 11 one cas number 23930 19 0 y pubchem cid 104845 iuphar bps 5461 drugbank db11371 y chemspider 94637 y unii bd07m97b2a kegg d07282 y chembl chembl190279 y comptox dashboard epa dtxsid9022576 echa infocard 100 164 405 chemical and physical data formula c 21 h 32 o 3 molar mass 332 484 g mol 1 3d model jsmol interactive image smiles o c2 c h 3 c h c h 1cc c h c o c c 1 c c2 cc c h 4c c h o cc c 34c inchi inchi 1s c21h32o3 c1 12 22 16 6 7 17 15 5 4 13 10 14 23 8 9 20 13 2 19 15 18 24 11 21 16 17 3 h13 17 19 23h 4 11h2 1 3h3 t13 14 15 16 17 19 20 21 m0 s1 y key duhuchoqidjxat olvmnogesa n y verify alfaxalone also known as alphaxalone or alphaxolone and sold under the brand name alfaxan and faxone is a neuroactive steroid and general anesthetic which is used currently in veterinary practice as an induction agent for anesthesia and as an injectable anesthetic 1 2 3 the most common side effect seen in current veterinary practice is respiratory depression when alfaxan is administered concurrently with other sedative and anesthetic drugs when premedications are not given veterinary patients also become agitated and hypersensitive when waking up alfaxalone works as a positive allosteric modulator on gaba a receptors and at high concentrations as a direct agonist of the gaba a receptor it is cleared quickly by the liver giving it a relatively short terminal half life and preventing it from accumulating in the body lowering the chance of overdose veterinary use edit alfaxalone is used as an induction agent an injectable anesthetic and a sedative in animals 4 while it is commonly used in cats and dogs it has also been successfully used in rabbits 5 horses sheep pigs and exotics such as red eared turtles axolotl green iguanas marmosets 6 and koi fish 7 as an induction agent alfaxalone causes the animal to relax enough to be intubated which then allows the administration of inhalational anesthesia premedication administering sedative drugs prior to induction reduces the required induction dose of alfaxalone 6 alfaxalone can be used for total intravenous anesthesia this is especially useful in airway procedures such as bronchoscopy to avoid exposing the clinician to volatile anesthetic 8 9 once the administration of alfaxalone stops the animal quickly recovers from anesthesia 10 alfaxalone can be used for intramuscular im sedation although higher doses may be precluded by the relatively large volume required 11 12 despite its use as an anesthetic alfaxalone itself has no analgesic properties 6 available forms edit though alfaxalone is not licensed for im or subcutaneous use in the united states as both cause longer recoveries with greater agitation and hypersensitivity to stimuli it is routinely used im in cats and is licensed as such in other countries 8 13 alfaxalone is dissolved in 2 hydroxypropyl β cyclodextrin 14 the cyclodextrin is a large starch derived molecule with a hydrophobic core where alfaxalone stays allowing the mixture to be dissolved in water and sold as an aqueous solution they act as one unit and only dissociate once in vivo 11 15 specific populations edit alfaxalone has been used to perform c sections in pregnant cats though it crosses the placental barrier and had some effects on the kittens there is no respiratory depression and no lasting effect alfaxalone has also been found to be safe in young puppies and kittens 16 17 alfaxalone has been noted to be a good anesthetic agent for dogs with ventricular arrhythmias and for sighthounds 13 18 there seems to be marked difference in sex response anaesthesia in the male rat requires about four times more than in the female 19 side effects edit the most common side effect of alfaxalone is respiratory depression in addition to apnea the most prevalent alfaxalone can also decrease the respiratory rate minute volume and oxygen saturation in the blood 17 alfaxalone should be administered slowly over a period of at least 60 seconds or until anesthesia is induced as quick administration increases the risk of apnea 4 13 alfaxalone has some depressive effects on the central nervous system including a reduction in cerebral blood flow intracranial pressure and body temperature 17 greyhounds who are particularly susceptible to anesthetic side effects can have decreased blood flow and oxygen supply to the liver 17 when no premedications are used alfaxalone causes animals especially cats to be agitated when recovering 8 13 dogs and cats will paddle in the air vocalize excessively may remain rigid or twitch and have exaggerated reactions to external stimuli such as light and noise for this reason it is recommended that animals recovering from anesthesia by alfaxalone stay in a quiet dark area 17 overdose edit the quick metabolism and elimination of alfaxalone from the body decreases the chance of overdose 10 it would take over 28 times the normal dose to cause toxicity in cats 11 such doses however can cause low blood pressure apnea hypoxia and arrhythmia caused by the apnea and hypoxia 11 pharmacology edit pharmacodynamics edit gaba a receptor and the location of various ligand binding sites alfaxalone is a neuroactive steroid derived from progesterone though it has no glucocorticoid or mineralocorticoid action 8 10 instead it works by acting on gaba a receptors 20 it binds to the m3 m4 domains of the α subunit and allosterically modifies the receptor to facilitate the movement of chloride ions into the cell resulting in hyperpolarization of the post synaptic nerve which inhibits actions potentials at concentrations over 1 micromolar 21 alfaxalone binds to a site at the interface between the α and β subunits near the actual gaba binding site and acts as a gaba agonist similar to benzodiazepines 17 22 alfaxalone however does not share the benzodiazepine binding site 23 and actually prefers different gaba a receptors than benzodiazepines do it works best on the α1 β2 γ2 l isoform 11 research suggests that neuroactive steroids increase the expression of gaba a receptors making it more difficult to build tolerance 22 pharmacokinetics edit alfaxalone is metabolized quickly and does not accumulate in the body its use as an induction agent thus doesn t increase the time needed to recover from anesthesia 8 10 if it administered more slowly by diluting it in sterile water less actual alfaxalone is needed 9 alfaxalone binds to 30 50 of plasma proteins 24 and has a terminal half life of 25 minutes in dogs and 45 minutes in cats when given at clinical doses 2 mg kg and 5 mg kg respectively the pharmacokinetics are nonlinear in cats and dogs 14 25 most alfaxalone metabolism takes place in the liver though some takes place in the lungs and kidneys as well 25 in the liver it undergoes both phase i cytochrome p450 dependent and phase ii conjugation dependent metabolism the phase i products are the same in cats and dogs allopregnatrione 3β alfaxalone 20 hydroxy 3β alfaxalone 2 hydroxyalfaxalone and 2α hydroxyalfaxalone 11 17 in dogs the phase ii metabolites are alfaxalone glucuronide the major metabolite 20 hydroxyalfaxalone sulfate and 2α hydroxyalfaxalone glucuronide in cats there is a greater production of 20 hydroxyalfaxalone sulfate than alfaxalone glucuronide cats also have 3β alfaxalone sulfate which is not present in dogs 11 17 alfaxalone is mostly excreted in the urine though some is excreted in the bile as well chemistry edit progesterone left and its derivative alfaxolan right the differences are highlighted in pink see also list of neurosteroids alfaxalone also known as 11 oxo 3α 5α tetrahydroprogesterone 5α pregnan 3α ol 11 20 dione or 3α hydroxy 5α pregnane 11 20 dione is a synthetic pregnane steroid and a derivative of progesterone 1 it is specifically a modification of progesterone in which the c3 ketone has been reduced to a hydroxyl group the double bond between the c4 and c5 positions has been reduced and is now a single bond and a ketone has been substituted at the c11 position 1 alfaxalone is also a derivative of allopregnanolone differing from it only by the addition of the c11 ketone 1 other closely related steroids include ganaxolone hydroxydione minaxolone pregnanolone and renanolone 1 history edit in 1941 progesterone and 5β pregnanedione were discovered to have cns depressant effects in rodents this began a search to make a synthetic steroid that could be used as an anesthetic most of these efforts were aimed at making alfaxalone more water soluble 22 in 1971 a combination of alfaxalone and alfadolone acetate was released as the anesthetics althesin for human use and saffan for veterinary use 6 25 the two were dissolved in cremophor el a polyoxyelthylated castor oil surfactant 14 althesin was removed from the market in 1984 for causing anaphylaxis it was later found that this was due to cremophor el which caused the body to release histamine rather than alfaxolone or alfadolone 6 13 22 saffan was removed from use for dogs only but stayed on for other animals none of which histamine release to the same extent that dogs did 26 it was still especially valued in cats for its lack of depressant effects on the cardiovascular system which made it three times less fatal than any other anesthetic on the market at the time 6 9 the release of histamine caused most cats 69 to have edema and hyperemia in their ears and paws 27 only some also got laryngeal or pulmonary edema 26 in 1999 a lyophilized form of alfaxalone was released for cats 11 the new drug alfaxan used a cyclodextrin as a carrier agent to make alfaxalone more water soluble rather than cremophor el 13 alfadolone was not included in the mixture as its hypnotic effects were quite weak 26 an aqueous form of alfaxan was released in australia in 2000 2001 and saffan was finally removed from the market in 2002 alfaxan was released in the uk in 2007 central europe in 2008 canada in 2011 and the united states in 2012 11 12 currently a human form of alfaxalone is in development under the name phaxan alfaxalone will be dissolved in 7 sulfo butyl ether β cyclodextrin which unlike the cyclodextrin used in alfaxan is not toxic to people 14 society and culture edit generic names edit alfaxalone is the inn tooltip international nonproprietary name ban tooltip british approved name dcf tooltip dénomination commune française and jan tooltip japanese accepted name of alfaxolone alphaxalone was the former ban of the drug 1 2 but this was eventually changed alphaxolone and alfaxolone are additional alternative spellings 1 2 3 28 brand names edit alfaxalone was marketed in 1971 in combination with alfadolone acetate under the brand name althesin for human use and saffan for veterinary use 17 29 althesin was withdrawn from the market in 1984 whereas saffan remained marketed 30 a new formulation containing alfaxalone only was introduced for veterinary use in 1999 under the brand name alfaxan 17 29 following the introduction of alfaxan saffan was gradually discontinued and is now no longer marketed 30 31 another new formulation containing alfaxalone alone is currently under development for use in humans with the tentative brand name phaxan 14 32 availability edit alfaxalone is marketed for veterinary use under the brand name alfaxan in a number of countries including australia belgium canada france germany ireland japan the netherlands new zealand south africa south korea spain taiwan the united kingdom and the united states 3 33 34 references edit 1 2 3 4 5 6 7 elks j 14 november 2014 the dictionary of drugs chemical data chemical data structures and bibliographies springer pp 664 isbn 978 1 4757 2085 3 1 2 3 morton ik hall jm 6 december 2012 concise dictionary of pharmacological agents properties and synonyms springer science business media p 11 isbn 978 94 011 4439 1 1 2 3 alfaxalone drugs com 1 2 alfaxan alfaxalone injection solution dailymed us national library of medicine retrieved july 15 2017 varga m 2014 chapter 4 anaesthesia and analgesia textbook of rabbit medicine 2nd ed butterworth heinemann pp 178 202 isbn 9780702049798 1 2 3 4 5 6 clarke kw trim cm hall lw eds 2014 chapter 6 general pharmacology of the injectable agents used in anaesthesia veterinary anaesthesia 11th ed oxford w b saunders pp 135 153 doi 10 1016 b978 0 7020 2793 2 00006 2 isbn 9780702027932 minter lj bailey km harms ca lewbart ga posner lp july 2014 the efficacy of alfaxalone for immersion anesthesia in koi carp cyprinus carpio veterinary anaesthesia and analgesia 41 4 398 405 doi 10 1111 vaa 12113 pmid 24754530 1 2 3 4 5 rezende m june 2015 reintroduced anesthetic alfaxalone pdf clinician s brief archived from the original pdf on july 23 2015 retrieved july 14 2017 1 2 3 clarke kw trim cm hall lw eds 2014 chapter 16 anaesthesia of the cat veterinary anaesthesia 11th ed oxford w b saunders pp 499 534 doi 10 1016 b978 0 7020 2793 2 00016 5 isbn 9780702027932 1 2 3 4 ferré pj pasloske k whittem t ranasinghe mg li q lefebvre hp july 2006 plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of alfaxan cd rtu veterinary anaesthesia and analgesia 33 4 229 36 doi 10 1111 j 1467 2995 2005 00264 x pmid 16764587 1 2 3 4 5 6 7 8 9 warne ln beths t whittem t carter je bauquier sh february 2015 a review of the pharmacology and clinical application of alfaxalone in cats veterinary journal 203 2 141 8 doi 10 1016 j tvjl 2014 12 011 hdl 11343 58687 pmid 25582797 1 2 zeltzman p november 17 2014 why administering alfaxalone requires a bit of education veterinary practice news retrieved july 14 2017 1 2 3 4 5 6 nieuwendijk h march 2011 alfaxalone veterinary anesthesia analgesia support group retrieved july 14 2017 1 2 3 4 5 absalom ar mason kp march 1 2017 total intravenous anesthesia and target controlled infusions a comprehensive global anthology springer pp 31 306 isbn 9783319476094 klöppel h leece ea january 2011 comparison of ketamine and alfaxalone for induction and maintenance of anaesthesia in ponies undergoing castration veterinary anaesthesia and analgesia 38 1 37 43 doi 10 1111 j 1467 2995 2010 00584 x pmid 21214708 bourne w august 1924 clarke kw trim cm hall lw eds chapter 19 anaesthesia for obstetrics canadian medical association journal anaesthesia in obstetrics 14 8 11th ed w b saunders 702 703 doi 10 1016 b978 0 7020 2793 2 00019 0 isbn 9780702027932 pmc 1707545 pmid 20315061 cite journal isbn date incompatibility help cs1 maint periodical has isbn link 1 2 3 4 5 6 7 8 9 10 grimm ka lamont la tranquilli wj greene sa robertson sa 2015 veterinary anesthesia and analgesia 5th ed john wiley sons pp 289 290 isbn 9781118526200 clarke kw trim cm hall lw eds 2014 chapter 15 anaesthesia of the dog veterinary anaesthesia 11th ed oxford w b saunders pp 135 153 doi 10 1016 b978 0 7020 2793 2 00015 3 isbn 9780702027932 fink g sarkar dk dow rc dick h borthwick n malnick s twine m july 1982 sex difference in response to alphaxalone anaesthesia may be oestrogen dependent natu...