ALFAXALONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H32O3
Molecular Weight	332.477
Optical Activity	UNSPECIFIED
Defined Stereocenters	8 / 8
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC(=O)[C@@]3([H])[C@@]2([H])CC[C@@]4([H])C[C@H](O)CC[C@]34C

InChI

InChIKey=DUHUCHOQIDJXAT-OLVMNOGESA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H32O3
Molecular Weight	332.477
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 8
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.alfaxan.co.uk/what-is-alfaxan
Curator's Comment: description was created based on several sources, including: http://www.vasg.org/pdfs/alfaxalone_vasg_05_11.pdf | https://www.fda.gov/downloads/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/UCM326904.pdf

Alfaxalone is a rapidly acting hydrophobic synthetic neurosteroid. It is indicated for the induction and maintenance of anesthesia and for induction of anesthesia followed by maintenance with an inhalant anesthetic, in cats and dogs. Alfaxalone induces anaesthesia through activity at the gamma amino butyric acid sub-type A receptor (GABAA) present on cells in the Central Nervous System (CNS). Alfaxalone enhances the effects of GABA at the GABAA receptors resulting in opening of channels into the cells and an influx of chloride ions. This causes hyperpolarisation of the cells and inhibition of neural impulse transmission. Alfaxalone can be safely combined with premedicants (xylazine, (dex)medetomidine, acepromazine, midazolam), opioids (morphine, methadone, hydromorphone, butorphanol, nalbuphine, buprenorphine, fentanyl), and NSAIDs. Alfaxalone’s adverse reactions are: hypotension, tachycardia, apnea, hypertension, bradypnea and others.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type II alpha subunit 27 Target ID: CHEMBL4187 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22538831	Blocker 537
Sodium channel protein type IV alpha subunit 23 Target ID: CHEMBL2072 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22538831	Blocker 537
GABAA receptor (Bovine) 1 Target ID: GABAA receptor (Bovine) Sources: https://www.ncbi.nlm.nih.gov/pubmed/3032320	Agonist 2678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f5d57f72-71e4-46af-b262-673ceabeff04	Primary		Approved 8429	Alfaxan Approved Use ALFAXAN is indicated for the induction and maintenance of anesthesia and for induction of anesthesia followed by maintenance with an inhalant anesthetic, in cats and dogs. Launch Date 2012

PubMed

Title	Date	PubMed
GABAA receptor subtypes: ligand binding heterogeneity demonstrated by photoaffinity labeling and autoradiography.	1993 Oct	8397295
Selective cyclodextrin inhibition of alfaxolone-induced ataxia.	1996 May	8799881
Identification of a human nuclear receptor defines a new signaling pathway for CYP3A induction.	1998 Oct 13	9770465
Influence of membrane cholesterol on modulation of the GABA(A) receptor by neuroactive steroids and other potentiators.	2001 Nov	11704651
Mutation of the GABAA receptor M1 transmembrane proline increases GABA affinity and reduces barbiturate enhancement.	2002 Mar	11955521
Pharmacological characterization of the homomeric and heteromeric UNC-49 GABA receptors in C. elegans.	2003 Mar	12642390
A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation.	2003 Oct 31	12939268
Quantification of collagen and proteoglycan deposition in a murine model of airway remodelling.	2005 Apr 8	15819978
Plasma pharmacokinetics of alfaxalone in dogs after an intravenous bolus of Alfaxan-CD RTU.	2006 Jul	16764587
In silico prediction of pregnane X receptor activators by machine learning approaches.	2007 Jan	17003167
Changes in relative potency among positive GABA(A) receptor modulators upon discontinuation of chronic benzodiazepine treatment in rhesus monkeys.	2007 May	17245585
A comparison of microbial growth in alfaxalone, propofol and thiopental.	2008 Apr	18194193
Clinical evaluation of alfaxalone in cyclodextrin for the induction of anaesthesia in rabbits.	2008 Sep 27	18820329
Use of alfaxalone in rabbits.	2009 Feb 7	19202182
Retinal afferents synapse with relay cells targeting the middle temporal area in the pulvinar and lateral geniculate nuclei.	2010	20179789
Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog.	2010 Jan	20017814

Patents

Sample Use Guides

In Vivo Use Guide

Induction of general anesthesia in cats: range 2.2 - 9.7 mg/kg for cats that did not receive a preanesthetic and 1.0 - 10.8 mg/kg for cats that received a preanesthetic. Induction of general anesthesia in dogs: range 1.5 - 4.5 mg/kg for dogs that did not receive a preanesthetic and between 0.2 - 3.5 mg/kg for dogs that received a preanesthetic.

Route of Administration: Intravenous

In Vitro Use Guide

Alfaxalone at a concentration of 50 uM reversibly blocked ongoing Seizure like events (SLEs) in organotypic hippocampal slice cultures. At a concentration of 20 uM it did not block ongoing SLEs but significantly reduced strength and duration of SLEs.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:28:07 GMT 2023` Edited by `admin` on `Fri Dec 15 15:28:07 GMT 2023`
Record UNII	BD07M97B2A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ALFAXALONE

Official Name

English

PHAXAN

Brand Name

English

ALFAXALONE [GREEN BOOK]

Common Name

English

GR 2/234

Code

English

ALFAXALONE [JAN]

Common Name

English

GR-2/234

Code

English

ALPHAXALONE

Common Name

English

ALFAXALONE [MI]

Common Name

English

alfaxalone [INN]

Common Name

English

ALFAXALONE [MART.]

Common Name

English

Alfaxalone [WHO-DD]

Common Name

English

3.ALPHA.-HYDROXY-5.ALPHA.-PREGNANE-11,20-DIONE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C245