The anesthetic site of action: from the intact brain to the isolated protein. An overview

Abstract

To the present day there is no consensus of opinion as to which molecular events lead to the complex clinical state generally referred to as anaesthesia. The multitude of simultaneous physiological changes are also responsible for this lack of consensus. During anaesthesia, for example, consciousness, perception, memory, pain, and muscle relaxation are altered. The actions of anaesthetics correlate very well with their partitioning into lipophilic phases. Lipophilic interactions are non-specific. Therefore, it is likely that anaesthetics act at many different sites. Cell membranes are not the only possible sites but also membrane proteins and the various hydrophobic domains they contain. The multitude of clinical anaesthetic effects is paralleled by the complexity of molecular interactions. A better understanding of anaesthesia requires an integrated view of anaesthetic effects at the various systemic levels, beginning with the molecular domain and ending with the intact central nervous system. Anaesthesia research could be directed more towards man because it has now become possible to conduct molecular in-vitro studies with human cells as well as non-invasive studies of the intact human central nervous system.