SHAPE SIMILARITY INDEXES ARE THE BEST PREDICTORS OF SUBSTITUTED FLUOROETHANE AND ETHER ANESTHESIA

Activity relationships were calculated for 18 substituted fluoroethane and ether inhalational anaesthetics using molecular shape similarity indices as the independent variables. The correlation coefficients for the models based on shape similarity ranged from 0.939-0.984, whereas the coefficients based on oil/gas solubilities were 0.005-0.512. The predictive ability of these relationships, determined by cross-validat ion, was also found to be significantly higher than that of convention al lipid solubility models and of relationships based on Van der Waals (VdW) surface areas. The shape similarity models accurately predict t he anaesthetic potencies of the enantiomers of a chiral ether, and act ivities of transitional compounds which deviate from the traditional M eyer-Overton rule. The results are discussed in terms of the molecular mechanisms of general anaesthetic action.