Mechanism of anesthetic action: oxygen pathway perturbation hypothesis

Although more than 150 years have passed since the discovery of general ane sthetics, precisely how they work remains a mystery. We propose a novel uni tary mechanism of general anesthesia verifiable by experiments. In the prop osed mechanism, general anesthetics perturb oxygen pathways in both membran es and oxygen-utilizing proteins, such that the availability of oxygen to i ts sites of utilization is reduced, which in turn triggers cascading cellul ar responses through oxygen-sensing mechanisms, resulting in general anesth esia. Despite the general assumption that cell membranes are readily permea ble to oxygen, existing publications indicate that these membranes are plau sible oxygen-transport barriers. The present hypothesis provides a unified framework for explaining phenomena associated with general anesthesia and e xperimental results on the actions of general anesthetics. If verified by e xperiments, the proposed mechanism also has other significant medical and b iological implications. (C) 2001 Harcourt Publishers Ltd.