[Mechanisms of the protective effect of methohexital on cerebral energy metabolism].

The purpose of the present investigation was to study the effect of alpha-(+/-)-5-allyl-1-methyl-5-(1-methyl-2-pentinyl) barbituric acid (methohexital, Brevimytal sodium) on brain energy metabolism. The model of the isolated perfused rat brain was used. The high-energy phosphates, some substrates of glycolysis and the intracellular distribution of hexokinase activity were measured in the cortical tissue of the isolated rat brain after 30 min of perfusion, after ischemia or anoxia and after various recovery periods. The EEG was recorded as a parameter of the neuronal activity. The following results were obtained: 1. Ischemia and anoxia accelerated the glycolysis rate which was inhibited by methohexital. 2. The energy metabolism was more rapidly normalized after ischemia or anoxia when methohexital was added to the perfusion medium (0.2 mmol/l). 3. Compared to the corresponding preparation, the spontaneous electrical activity of the isolated brain was maintained in ischemia or anoxia for a longer period and appeared again more rapidly in the recovery periods when methohexital was present. 4. Phosphofructokinase activity was inhibited by methohexital in the recovery period after ischemia or anoxia, respectively. 5. Inhibition of hexokinase activity predominated in the surgical stage of anesthesia when glycolysis rate was not accelerated. Methohexital seemed to inhibit hexokinase activity by solubilizing the mitochondrial bound form.