Physicochemical Aspects of the Action of General Anaesthetics

Abstract

THE physicochemical aspects of the action of anaesthetics have been studied for many years, with general agreement on the following conclusions. No chemical reaction seems to take place as in the extreme case of rare gases anaesthesia can be realized under proper conditions¹. Observations favour the membrane as the site of anaesthetic action², and the anaesthetic receptor seems to be of finite size and the anaesthetic agents molecules of limited size. It has been suggested that narcosis occurs when a critical fraction of space in the membrane is occupied by the volatile anaesthetic agent and it is generally agreed that narcosis is due to physical rather than chemical action of the molecule³. Relatively weak physical forces are involved and these are frequently thought to be associated with the London dispersion force⁴. Not surprisingly there is good correlation between anaesthetic potency and molar refraction⁵, polarizability of the anaesthetic agent⁶, molal volume, solubility in olive oil^7–10, boiling points, and other properties of the molecules that are decided by the relatively weak long range interactions. Correlation of anaesthetic activity with the van der Waals a and b constants¹¹ is of particular interest here. The constant a is associated with the cohesive forces between molecules, and b with their volumes. The qualitative correlation of the van der Waals constants with anaesthetic potency has been discussed by Wulf and Featherstone¹¹. Wilson et al.¹² demonstrated the correspondence between isonarcotic pressure of inert gases and increased hydrolysis of choline esters expressed as a function of √a.