Pharmacodynamics GABAA receptor and the location of various ligand-binding sites.<unk>  is a neuroactive steroid derived from progesterone, though it has no glucocorticoid or mineralocorticoid action. Instead, it works by acting on GABAA receptors. 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,<unk>  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.<unk> , however, does not share the benzodiazepine binding site, and actually prefers different GABAA receptors than benzodiazepenes do. It works best on the α1-β2-γ2-L isoform. Research suggests that neuroactive steroids increase the expression of GABAA receptors, making it more difficult to build tolerance. Pharmacokinetics<unk>  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. If it administered more slowly by diluting it in sterile water, less actual<unk>  is needed.<unk>  binds to 30–50% of plasma proteins, 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. Most<unk>  metabolism takes place in the liver, though some takes place in the lungs and kidneys as well. 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. In dogs, the phase II metabolites are<unk>  glucuronide (the major metabolite), 20-hydroxyalfaxalone sulfate, and 2α-hydroxyalfaxalone glucuronid. In cats, there is a greater production of 20-hydroxyalfaxalone sulfate than<unk>  glucuronide; cats also have 3β-alfaxalone-sulfate, which is not present in dogs.<unk>  is mostly excreted in the urine, though some is excreted in the bile as well.
Alfaxalone
Metaxalone
Guaifenesin
Bethanechol
Butalbital
Benzoctamine
Pseudoephedrine
Ephedrine