Alfaxolone/alfadolone (brand names Althesin (

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

), Saffan ( veterinary) is a short acting intravenous anaesthetic agent. It was withdrawn from the market due to severe drug reactions. It is composed of a 3:1 mixture of

alfaxalone Alfaxalone, also known as alphaxalone or alphaxolone and sold under the brand name Alfaxan, is a neuroactive steroid and general anesthetic which is used currently in veterinary practice as an induction agent for anesthesia and as an injectab ...

and

alfadolone Alfadolone (INN), or alphadolone is a neuroactive steroid and general anesthetic. Along with alfaxolone, as alfadolone acetate, it is one of the components of the anesthetic drug mixture althesin. Chemistry See also * Ganaxolone * Hydroxydion ...

, two neurosteroids.

Mechanism

Alfaxolone/alfadolone is short-duration, intravenous anaesthetic made from a combination of two steroidal compounds, alfaxalone and alfadolone of which the former is the primary anaesthetic agent. Alfadolone acts to increase the solubility of the mixture in which it is dissolved, a polyethylated castor oil

adjuvant In pharmacology, an adjuvant is a drug or other substance, or a combination of substances, that is used to increase the efficacy or potency of certain drugs. Specifically, the term can refer to: * Adjuvant therapy in cancer management * Analgesic ...

. Anaesthetic efficacy is achieved by allosteric potentiation of the GABA_A chloride channel to produce 'fast' synaptic inhibition.

Clinical use

Alfaxolone/alfadolone is short-acting, rapid onset anaesthetic which has been used for out-patient surgery. It does not have significant analgesic properties and anaesthesia has often been maintained with inhalational anaesthetics such as

halothane Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

. These have also been accompanied by

neuromuscular blockers Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished via their action on the post-synaptic acetylcholine (Nm) receptors. In clin ...

. Procedures carried out under this drug are greatly varied and have included orthopaedic, gynaecological, dental and urological surgery. Notable effects include a drop in arterial and venous pressure in a quarter of patients; this is accompanied by a compensatory mild tachycardia in around 35% of those observed in a population skewed towards geriatrics.

Cremophor EL Kolliphor EL, formerly known as Cremophor EL, is the registered trademark of BASF Corp. for its version of polyethoxylated castor oil. It is prepared by reacting 35 moles of ethylene oxide with each mole of castor oil. The resulting product is a mi ...

(aka. Polyoxyl 35 Castor Oil, a surfactant and derivative of castor oil) was the solubilizing agent (excipient / additive) of Althesin. A study 2001 found that Cremophor EL, when previously used as a solubilizing agent in lipid emulsions, was responsible for severe anaphylactoid reactions. Drugs using it were reformulated to use other emulsifiers. Alfaxolone/alfadolone has been re-branded as "Saffan" and is available for use in veterinary anaesthesia.

References

{{DEFAULTSORT:Alfaxolone alfadolone General anesthetics Neurosteroids Combination drugs GABAA receptor positive allosteric modulators Pregnanes