Posted by ed_uk on March 20, 2005, at 19:40:31
Hello everyone!
Flumazenil is widely used as a benzodiazepine antagonist, a benzo 'antidote' or whatever you want to call it. It blocks benzodiazepine receptors and reverses the acute effects of benzodiazepines. It is used in the ICU to wake people up after they have been sedated with a benzo. It is also used to wake people up after surgery when benzos have been used during the operation. It is occasionally used to treat benzo overdose. The manufacturer warns that the administration of flumazenil to patients on long-term benzo treatment may abruptly precipitate withdrawal symptoms, this is because it acts as a competitive antagonist ie. it can displace benzodiazepines from their receptors. Strangely, flumazenil is not always capable of precipitating withdrawal symptoms.
The administration of flumazenil to patients with anxiety disorders has been reported to provoke panic.
Under some conditions, flumazenil may act as a benzodiazepine partial agonist, with weak intrinsic activity. Under other circumstances, it might actually function as a partial inverse agonist with weak intrinsic activity. When administered to a patient who has been given a benzo, it effectively functions as an antagonist.
In rats, flumazenil can reduce anxiety due to ethanol withdrawal. It has been suggested than flumazenil may be antagonising the effects of an endogenous benzodiazepine inverse agonist.
Below is a very interesting study. It has been hypothesised that flumazenil treatment may help to 'normalise' GABAergic function in patients undergoing benzodiazepine withdrawal - as a result, flumazenil may have a role in the treatment of benzodiazepine physical dependence.
Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo-controlled study.
Flumazenil (FLU), a benzodiazepine (BZD) partial agonist with a weak intrinsic activity, was previously found unable to precipitate withdrawal in tolerant subjects submitted to long-lasting BZD treatment. The potential use of FLU to treat BZD withdrawal symptoms has also been evaluated tentatively in clinical studies. In the present experiment, FLU (treatment A) was compared with oxazepam tapering (treatment B) and placebo (treatment C) in the control of BZD withdrawal symptoms in three groups of BZD dependent patients. Group A patients (20) received FLU 1 mg twice a day for 8 days, and oxazepam 30 mg in two divided doses (15 mg + 15 mg) during the first night, oxazepam 15 mg during the second night and oxazepam 7.5 mg during the third night. FLU was injected i.v. in saline for 4 hours in the morning and 4 hours in the afternoon, in association with placebo tablets. Group B patients (20) were treated by tapering of oxazepam dosage (from 120 mg) and with saline solution (as placebo) instead of FLU for 8 days. Group C patients (10) received saline instead of FLU and placebo tablets instead of oxazepam for 8 days. FLU immediately reversed BZD effects on balance task and significantly reduced withdrawal symptoms in comparison with oxazepam and placebo on both self-reported and observer-rated withdrawal scales. The partial agonist also reduced craving scores during the detoxification procedure. In addition, during oxazepam tapering, group B patients experienced paradoxical symptoms that were not apparent in FLU patients. Patients treated with FLU showed a significantly lower relapse rates on days 15, 23 and 30 after the detoxification week. Our data provide further evidence of FLUs ability to counteract BZD effects, control BZD withdrawal and normalize BZD receptor function. The effectiveness of FLU may reflect its capacity to upregulate BZD receptors and to reverse the uncoupling between the recognition sites of BZD and GABA, on the GABA(A) macromolecular complex, that has been reported in tolerant subjects.
I would love to hear your comments. Flumazenil has also been proposed as a treatment for protracted benzodiazepine withdrawal, where neurological symptoms persist long after the drug is discontinued. It is thought that flumazenil might be able 'reset' benzodiazepine receptor function.
/Ed
poster:ed_uk
thread:473333
URL: http://www.dr-bob.org/babble/wdrawl/20050228/msgs/473333.html