Concentrations Of Alphaxalone Research Articles

EFFECTS OF METHOHEXITONE, ALTHESIN, KETAMINE AND DROPERIDOL ON PERIPHERAL VAGAL TRANSMISSION

The effects of methohexitone, ketamine, Althesin and droperidol on the peripheral vagal transmission to the heart were studied in decerebrate cats by evaluating the influences of the drugs on the heart rate responses to vagal electrostimulation and the injection of acetylcholine i.v. The sites of the peripheral vagal transmission (vagal ganglia and sino-atrial pacemaker cells) were reached by the application of the drugs to the pericardial space. The bradycardia in response to vagal electrostimulation was attenuated by Althesin (2.1 x 10(-4)-3.3 x 10(-3) mol litre-1; expressed as the concentration of alphaxalone), ketamine (2.9 x 10(-4)-4.6 x 10(-3) mol litre-1) and droperidol (2.6 x 10(-5)-6.6 x 10(-4) mol litre-1) in a concentration-dependent manner, but not influenced by methohexitone (2.8 x 10(-4)-4.4 x 10(-3) mol litre-1). The bradycardia-attenuating effects were probably caused by an atropine-like action since the heart rate responses to the injection of acetylcholine i.v. were also attenuated by the same three drugs.

Metabolism of the steroid anaesthetic alphaxalone by the isolated perfused rat lung.

Abstract We have investigated the metabolism of the steroid anaesthetic, alphaxalone (3α-hydroxy-5α-pregnane-11, 20-dione), in the isolated rat lung perfused at 10ml min−1 with the plasma substitute, Haemaccel. When [14C]-alphaxalone was introduced into the perfusate during a 90 min recirculating perfusion, four metabolites appeared in the reservoir. We have identified two of these by gas chromatographic-mass spectrometric (GC-MS) methods as 3α,11-dihydroxy-5α-pregnane-20-one (metabolite 2), the major metabolite and 5α-pregnane-3α, 11,20-triol (metabolite 3); precise assignment of the stereochemistry at C11 and C20 was not possible. Following perfusion of up to 30 min with concentrations of alphaxalone ranging from 0.08 to 8.9 μM, we have measured metabolite 2 in both the lung tissue and in the reservoir. From this data we have obtained a Km of 0.25 μ and a Vmax of 7.8 nmol min−1 g dry lung−1. Extrapolating from reported plasma concentrations in humans, it would seem that this ability of the lung to metabolize alphaxalone would have tittle influence during induction of anaesthesia. However, it could significantly influence the concentration of alphaxalone in the cerebral circulation during administration of the considerably lower doses of alphaxalone used for sedation during regional anaesthesia.