Effects of sodium valproate and acetazolamide on cerebral respiration

The effects of sodium valproate and acetazolamide on the oxygen uptake of guinea pig brain cortex slices were investigated. In calcium-free medium, sodium valproate inhibited the oxygen uptake appreciably in the presence of glucose and glutamic acid. Acetazolamide, on the other hand, was more effective in inhibiting oxygen uptake in the presence of glucose than in the presence of glutamic acid. Addition of 0.2 mM CaCl2 in the medium containing 5 mM KCl could appreciably reverse the inhibition of oxygen uptake by acetazolamide in the presence of glucose. The inhibition of oxygen uptake by these drugs in the presence of glucose, however, could be completely reversed by increasing the dose of K+ ions (100 mM) in the medium which had no effect on the inhibition of oxygen uptake in the presence of glutamic acid. When the concentration of Ca2+ ions in the medium was elevated to 0.75 mM, the inhibitory effects of these drugs on the oxygen uptake in the presence of both glucose and glutamic acid could be completely abolished. Sodium valproate also inhibited the endogenous respiration of guinea pig brain cortex slices, whereas acetazolamide was almost without any effect. Increase in the concentration of Ca2+ ions in the medium failed to counteract the inhibition of endogenous respiration of guinea pig brain cortex slices by sodium valproate.