Isoflurane and sevoflurane may act as metabolic inhibitors by depolarizing pre-synaptic mitochondria through inhibition of the electron transport chain, although isoflurane seems to inhibit mitochondrial function more significantly than sevoflurane. Both agents inhibit the respiratory chain sufficiently to cause ATP synthase reversal.

Sevoflurane and propofol at equipotent doses depolarize the mitochondria in rat and human nerve terminals to the same extent. The depolarizing effect of propofol on Psi(m) was more rapid in onset than that of sevoflurane. Whereas sevoflurane inhibits the respiratory chain sufficiently to cause ATP synthase reversal, the depolarizing effect of propofol seems to be related to inhibition of the respiratory chain from complex I to V.

Significantly higher levels of excitatory amino acids in striatum, significantly lower mean arterial pressure, and a significantly greater degree of hypoperfusion in cerebral cortex were found after reoxygenation with 21% oxygen compared with 100% oxygen in normocapnic, hypoxemic-ischemic newborn piglets. This suggests a less favorable outcome in the group receiving room air.

These results indicate that different volatile anaesthetics may act differently on the presynaptic terminal. The exact modes of action have to be further investigated.