title: Selective cyclodextrin inhibition of alfaxolone-induced ataxia.
abstract: 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.
authors.affiliation: Behavioral Pharmacology Laboratory/Psychiatry Service 116A, VA Medical Center, Washington, DC 20422, USA.
authors.forename: L
authors.initials: L
authors.lastname: Koetzner
authors.forename: R L
authors.initials: RL
authors.lastname: Riggs
authors.forename: J
authors.initials: J
authors.lastname: Mastropaolo
authors.forename: S I
authors.initials: SI
authors.lastname: Deutsch
mesh_terms: D000818:Animals; D001259:Ataxia / Q000139:chemically induced*; D003505:Cyclodextrins / Q000494:pharmacology*; D003975:Diazepam / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D051379:Mice; D014677:Pharmaceutical Vehicles; D010938:Plant Oils / Q000494:pharmacology; D011277:Pregnanediones / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D011409:Propylene Glycols / Q000494:pharmacology; D012997:Solvents
chemical_list: D003505:Cyclodextrins; D014677:Pharmaceutical Vehicles; D010938:Plant Oils; D011277:Pregnanediones; D011409:Propylene Glycols; D012997:Solvents; D000431:Ethanol; C006477:alphaxalone; D003975:Diazepam