Ondo WG and Silay YS (2006) Intravenous flumazenil for Parkinson's disease: a single dose, double blind, placebo controlled, cross-over trial. Mov Disord [doi: 10.1002/mds.21022]

Researchers from Baylor College of Medicine in Houston, TX, previously showed in an open-label trial that a 0.5 mg intravenous dose of the nonselective γ-aminobutyric (GABA) antagonist flumazenil was well tolerated and improved motor symptoms in patients with Parkinson's disease (PD). They have now replicated the results in a placebo-controlled, crossover trial, using a higher 1 mg dose.

In this study, eight subjects were initially randomized to receive flumazenil and eight to receive placebo. Finger-tapping tests were performed at baseline and for 90 min following infusion, at 15 min intervals. Following a 90 min washout, the medications were reversed. Change in tapping speed from baseline was significantly improved in subjects who received flumazenil compared with those who received placebo (P <0.0001); improvement was seen at every time point (P <0.01) except 15 min following infusion. Although Unified Parkinson's Disease Rating Scale (UPDRS) score improved more in the flumazenil group (particularly for bradykinesia and rigidity), this finding was not significant. Half of the subjects reported light-headedness, dizziness or wooziness on flumazenil, but the drug was generally well tolerated.

Proposed explanations for flumazenil's effect include normalizing of thalamic and pedunculopontine nucleus activity, improving output from the basal ganglia, and direct activation of the cortex. The authors acknowledge that intravenous flumazenil is unlikely to become a practical therapy for PD, but its proposed mechanisms of action warrant further investigation and indicate that GABA antagonists could be a novel potential treatment class for this condition.