FLUMAZENIL IN ALCOHOL-WITHDRAWAL - A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

The purpose of the present study was to study gamma-aminobutyric acid (GABA)-A receptor function in alcohol-dependent subjects during withdr awal, using the benzodiazepine antagonist flumazenil. In particular, w e wanted to examine the hypotheses that an endogenous inverse agonist ligand at the GABA-A benzodiazepine receptor (GBzR) is active during w ithdrawal (in which case flumazenil should be anxiolytic), or whether chronic alcohol intake results in a shift in sensitivity of the recept or in the inverse agonist direction (in which case flumazenil should b e anxiogenic). Results from 15 alcohol-dependent subjects in a double- blind placebo-controlled cross-over study showed that flumazenil was n either anxiolytic nor anxiogenic, although withdrawal scores were redu ced during the course of the study. The fact that flumazenil was not a nxiogenic, as it is in panic disorder, suggests that the GBzR is funct ioning differently in these two clinically similar conditions.