This study will investigate the effects of the drug flumazenil on brain excitability and the
drug's relationship to a natural brain chemical called GABA. Flumazenil is commonly used in
hospitals to reverse the effects of a group of drugs called benzodiazepines, one of which is
Valium. Benzodiazepines act by enhancing the effects of GABA.
Healthy volunteers 21 years of age and older may be eligible for this study. Candidates
will be screened with a medical history and physical and neurological examinations.
Participants will have transcranial magnetic stimulation (TMS) four times on two different
days, before and after receiving an intravenous (through a vein) infusion of either
flumazenil or placebo (an inactive sugar solution), as follows:
TMS study 1
Drug or placebo infusion
TMS study 2 - 15 minutes after infusion
TMS study 3 - 60 minutes after infusion
TMS study 4 - 120 minutes after infusion
In transcranial magnetic stimulation, a very brief electrical current is passed through an
insulated coil wire placed on the scalp. These currents stimulate the cortex (outer part of
the brain). They may cause muscle, hand, or arm twitching if the coil is near the part of
the brain that controls movement, or they may affect other reflexes or movements. During
the study, subjects may be asked to make movements, do simple tasks or tense muscles. To
record the electrical activity of muscles, electrodes will be taped to the skin over the
muscles tested. In some cases, the studies will be videotaped.
Flumazenil will be infused through a catheter (thin plastic tube) attached to a needle
placed in an arm vein. On one day, subjects will receive a 1-mg injection of flumazenil
followed by a continuous infusion of 0.5 mg of the drug for about 30 minutes. On the other
day, they will receive placebo, administered in the same manner.
The purpose of this study is to investigate the effects of flumazenil on cortical
excitability in healthy human volunteers. Flumazenil acts as a potent benzodiazepine
(BZP)-specific antagonist by competing at the central synaptic gamma-aminobutyric acid
(GABA) receptor site. However, the relationship between GABA and flumazenil without BZPs is
not well known. We plan to determine if intravenous (IV) administration in therapeutic
dosage alters cortical excitability as measured by transcranial magnetic stimulation (TMS).
The long-term plan is to identify a pharmacological method to reduce cortical inhibition
that might be useful in stroke rehabilitation.
Only healthy volunteers, who are age 21 or older.
No history of surgery with metallic implants or known metallic particles in the brain.
Patients cannot be pregnant (as tested with a pregnancy test).
Patients with a psychiatric illness are not eligible.
No history of seizures.
No cardiovascular disease or drug therapy for chronic depression.
No hypersensitivity to benzodiazepines and related drugs.
No history of drug abuse and/or chronic alcoholism.