Effect of alphaxalone, a new intravenous anaesthetic, on oxidative phosphorylation in rabbit brain mitochondria

The effects of alphaxalone, a new intravenous anaesthetic, on mitochondrial reactions are described. At low concentrations (20–100 μM) the compound was found to be an inhibitor of the oxidation of NAD + -linked substrates in rabbit brain mitochondria. It was concluded that the site or action was at, or near, the rotenone-sensitive site on the NADH dehydrogenase enzyme system. When succinate was substrates, and when higher concentrations (300 μM) were used, alphaxalone was found to release respiratory control, stimulate state 4 respiration, relieve oligomycin-inhibited state 3 respiration and stimulate the mitochondrial ATPase. It was concluded that this second effect was due to an uncoupling action.