Two theories of the molecular mechanism of volatile anaesthetic action suggest either that anaesthetics cause a generalized perturbation of neuronal membrane structure, probably through a nonspecific interaction with membrane lipids1,2, or that anaesthetics bind to sets of sites of appropriate molecular dimension on membrane proteins3-5. Based on the recent finding that fluorinated anaesthetics can be observed in animal tissue by 19F nuclear magnetic resonance (19F-NMR) spectroscopy 6, we have used 19F-NMR to quantify the interaction between the volatile anaesthetic halothane and rat brain tissue. Steady-state brain halothane concentration was found to be a non-linear function of inspired concentration, with apparent saturation of brain occurring at inspired halothane concentrations above 2.5% by volume. Using a spin-echo pulse sequence it was found that halothane exists in two distinct chemical environments in brain, characterized by different spin-spin -relaxation times (T2), chemical shifts and kinetics of occupancy. Halothane concentration in one of these environments (T2=3.6ms) was saturated at ∼2.5% inspired halothane; occupancy of this environment was found to correlate with the anaesthetic effect of the drug. In the other environment (T2=43 ms), brain halothane concentration was a linear function of inspired concentration. These data suggest the existence of a saturable anaesthetic site for halothane in brain and do not support the concept that anaesthetics act by nonspecific membrane perturbation.
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