Specific actions of general anesthetics at molecular and cellular levels

ABSTRACT

Up to the present, and despite a widespread approach to explain the cellular and molecular basis of general anesthesia, the complex state of narcosis is still not completely understood. The continuing search for the mechanisms of action is prompted both by the clinical importance of these drugs and by the recognition that the work is related to basic studies of the brain, which represents the most important system in man. The observation that pressures of the order of 150 atmospheres restores consciousness to an anesthetized animal has very long been central to theories of the molecular mechanisms underlying general anesthesia. Many workers have argued that, because pressure can only act by reducing volume, anesthetics must be exerting their effects by increasing the volume of the cell membrane. Furthermore, it has been known for decades that anesthetics perturb the phospholipid bilayer of the cell membrane in proportion to their lipid solubility. However, recent neurophysiological, biochemical and pharmacological work has focused on membrane proteins in the single neuron, the smallest functional unit in the central nervous system [CNS]. In this review, the effects of intravenous and inhalational general anesthetics on ion channels and synaptic transmissions potentially relevant to the phenomena of anesthesia are described including the conflict between the classic lipid and the modern protein theories. The review will concentrate especially on the postsynaptic ligandgated ion-channels