Relationship of anesthetic activity of alkyl acetates to hydrophobicity and in vivo effect on membrane fluidity in mice

Abstract

In vivo anesthetic activity of alkyl acetates in mice was studied in relation to hydrophobicity and the in vivo effect on membrane fluidity. The anesthetic potency (AD₅₀) of alkyl acetates was determined; AD₅₀ shows the i.p. dose required to anesthetize 50% of mice from the treated group. We used log P (n-octanol/water partition coefficient) as an operational definition of hydrophobicity. Membrane fluidity was determined using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe. Log (1/AD₅₀) was a parabolic function of log P, and the value of log P that corresponds to the minimum AD₅₀ was estimated to be 2.08. Brain synaptosomal membranes were prepared from mice 30 min after dosing with each of the three alkyl acetates applied at 1.5-fold AD₅₀: n-butyl, n-amyl, and n-hexyl acetate. In each alkyl acetate group, most of the animals were anesthetized (>68%). Decreased membrane fluidity was observed for the animals that were anesthetized while no change in the fluidity was seen for the animals that were not anesthetized. The results suggest an involvement of decreased DPH fluidity in alkyl acetate-induced anesthesia.