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Section IICoredrugs in anaesthetic practicelog MACXeN 2 ODesfluraneSevoflurane
Enflurane
Isoflurane
HalothaneMethoxyfluranelog Oil:Gas partition coefficient
Figure 8.1.Straight line relationship between MAC and an index of lipid solubility (note:
logarithmic scales).Initially it was suggested that anaesthetic agents could penetrate the bilayer and
alter the molecular arrangement of the phospholipids, which led to expansion of
the membrane and disruption of the function of membrane-spanning ionic chan-
nels. Calculations identifying the volume of anaesthetic agent required to expand
membranes led to a “critical volume hypothesis”. Against such a theory, a 1◦Crise
in temperature increases membrane thickness to a similar extent as that seen with
volatile agents, yet increased temperature does not enhance anaesthesia – the oppo-
site is true.
A further theory suggested anaesthetic agents act at specific lipid site(s). The com-
position of phospholipids in the immediate vicinity of ion channels is different from
that of the general lipid bilayer. This proposed disruption of annular lipids associated
with specific ion-channels led to the perturbation theory.
Arapid advance in receptor protein identification within the central nervous sys-
tem has led to newer theories based on interactions with specific proteins. It now
seems likely that the correlation between potency and lipid solubility reflects the
lipophilic nature of specific protein-based binding site(s).Protein site(s) of action
Ligand-gated ionic channels are more sensitive to the action of general anaesthetics
than are voltage-gated channels. The interaction at inhibitory (GABAAand glycine)
and excitatory (neuronal nicotinic and NMDA) channels have all been studied. Table
8.1summarizes the relative activity of a number of agents at these receptors.