Selective cyclodextrin inhibition of alfaxolone-induced ataxia

The effect of the use of a number of popular solubility treatments was examined on alfaxolone- and diazepam-induced ataxia. The effects of diazepam were not significantly altered by solution in cyclodextrin, Alkamuls EL-620 or a mixture of propylene glycol and ethanol. The effects of alfaxolone were not altered by solution in Alkamuls EL-620, but were significantly lessened by solution in cyclodextrin. In a dose-response experiment, the ED50 of alfaxolone increased from 15.3 mg kg-1 (in Alkamuls EL-620) to 25.6 mg kg-1 (in hydroxypropyl-beta-cyclodextrin). The results suggest that although cyclodextrins are popular and effective solubilizers, their use must be considered carefully in the context of the experiments in which they are to be used.