GABAAbenzodiazepine receptor (GBzR) sensitivity: test-retest reliability in normal volunteers

Abstract

Rationale: Alcohol, benzodiazepines and barbiturates act through the GABA(A) benzodiazepine receptor (GBzR). Patients with some forms of anxiety disorder have reduced GBzR sensivity, although it is not clear whether this is a state or a trait phenomenon. We have developed a paradigm for assessing GBzR sensitivity using slowing of saccadic eye movements in response to intravenous midazolam.Objectives: To obtain reliability data for GBzR sensitivity in normal volunteers and to look at factors that might influence sensitivity.Methods: Five male volunteers received an intravenous infusion of midazolam (50 &mgr;m/kg) given over 10 min. Saccadic eye movement velocity (SEMV) was recorded at baseline and at 15 min intervals up to 120 min post infusion. Blood was taken at these times for mixazolam assay. The study was repeated at 4 weeks. Pharmacodynamic (PD) effect was calculated by measuring area under the curve (AUC) of SEMV plot versus time for each individual on both study days. Pharmacokinetic (PK) effect was calculated by measuring AUC from t = 0 to t = 120 min. Ratio of PD/PK effect was then calculated to give a measure of GBzR sensitivity.Results: There was a very strong correlation between individual GBzR sensitivity on both study days (r = 0.99; p = 0.008).Conclusion: The results suggest that GBzR sensitivity is relatively stable over time in normal volunteers and that the paradigm described has good reliability. Copyright 2000 John Wiley & Sons, Ltd.