A comparison of the effects of a subtype selective and non-selective benzodiazepine receptor agonist in two CO2 models of experimental human anxiety

AbstractStudies in human volunteers that can demonstrate proof of concept are attractive in that possible mechanisms and potential new drug treatments can be examined. We have been developing models of anxiety disorders using the inhalation of 7.5% CO2 for 20 min to model generalised anxiety disorder, as well as using the previously reported 35% CO2 as a model for panic anxiety. In a double-blind, placebo-controlled, three-way crossover study in 12 healthy volunteer subjects, we compared a full agonist at the benzodiazepine receptor that binds to four α-subtypes of the receptor (α-1,-2,-3,-5) (alprazolam 1 mg), with zolpidem (5 mg), an agonist selective for the α-1 subtype of the gamma amino butyric acid-receptor subtype A (GABA-A) receptor, which is a widely used hypnotic drug. Compared with placebo, both drugs significantly attenuated peak CO2-induced changes in subjective feelings after the inhalation of 7.5% CO2 for 20 min. However, there were fewer significant differences after a single vital capacit...