Physical Mechanisms of Anesthesia

It still remains unclear how anesthetics exert their pharmacological effects on excitable tissues and produce the physiological phenomenon known as anesthesia. The study of the mechanism of anesthetics is as old as anesthesia itself. The literature on this subject has developed for over a century. One of the major problems in developing a theory of the mechanism for these agents is the failure to define a structural requirement for activity; the other is the complexity of the system affected, the central nervous system (CNS). At one end of the spectrum, there is the complexity of the central nervous system, primarily due to the histological heterogeneity of the different cell types that comprise the CNS (l). At the other end is the complexity of the structure and function of the basic cellular membrane, which may also vary with cell types (1). Anesthesia can be produced by a wide variety of chemical agents, ranging from inert rare gases to steroid molecules (2, 3). The diversity of chemical structure of anesthetics suggests a lack of a specific receptor site, but the excellent correlation of lipid solubility with potency implies an interaction with hydrophobic regions in the membrane. Since physical properties such as lipid solubility are governed by intermolecular forces (4, 5), these proper­ ties, compared to anesthetic potency, have been the primary focus of re­ search into the physical mechanisms of anesthesia and have led to the basis for a unitary theory of anesthesia which suggests that all anesthetics act via