Hydrogen bonding in mechanisms of anaesthesia tested with chloroform and deuterated chloroform.

There has been recent speculation about the role of hydrogen bonding in molecular mechanisms of anaesthesia. We have tested this hypothesis by comparing the potencies of chloroform and deuterated chloroform in mice, using loss of righting reflex as the endpoint for anaesthesia. We found that the ED50 for chloroform was 0.297 +/- 0.03% (SD) and for deuterated chloroform 0.318 +/- 0.02% (SD). These values are not significantly different. However, there were some differences in toxicity with deuterated chloroform having less "acute" toxicity. This is compatible with an isotope effect in which deuterium interferes with the formation of reactive free radicals. We conclude from the potency data that hydrogen bonding can be excluded as the major mechanism of chloroform anaesthesia.