Mechanism of anesthetic action: oxygen pathway perturbation hypothesis.

Although more than 150 years have passed since the discovery of general anesthetics, precisely how they work remains a mystery. We propose a novel unitary mechanism of general anesthesia verifiable by experiments. In the proposed mechanism, general anesthetics perturb oxygen pathways in both membranes and oxygen-utilizing proteins, such that the availability of oxygen to its sites of utilization is reduced, which in turn triggers cascading cellular responses through oxygen-sensing mechanisms, resulting in general anesthesia. Despite the general assumption that cell membranes are readily permeable to oxygen, existing publications indicate that these membranes are plausible oxygen-transport barriers. The present hypothesis provides a unified framework for explaining phenomena associated with general anesthesia and experimental results on the actions of general anesthetics. If verified by experiments, the proposed mechanism also has other significant medical and biological implications. Copyright 2001 Harcourt Publishers Ltd.