To obtain drugs which are more selective at benzodiazepine (BZD) receptors, design and synthesis of functionally selective ligands for BZD receptors is the current strategy of our pharmaceutical chemistry department. The affinity of newly synthesized ligands is assessed by radioligand receptor binding assays. Based on our previous studies, 2-phenyl-5-oxo-7-methyl-1,3,4-oxadiazolo[a,2,3]-pyrimid...

Flumazenil is a specific benzodiazepine (BZD) antagonist which inhibits the effects of BZD agonists by competing for the receptor site in the central nervous system. It has completed clinical trials in the United States and received final approval from the U.S. Food and Drug Administration for release in January 1992. Following intravenous injection, clinically apparent arousal usually occurs w...

This study was conducted to evaluate the sedative effects of Arachis hypogaea L. stem and leaf extract (AHSLE) and determine its effect pathways through γ-aminobutyric acid (GABA)-gated channels on male Sprague-Dawley rats treated with pentobarbital. AHSLE was obtained from 98°C water (3 h, extracted twice). AHSLE and flumazenil (a GABA type A receptor antagonist) were administered to the rats ...

We performed a randomised, crossover study to investigate the effects of intravenous sedation on grip strength and bite force. Twenty male volunteers received a bolus intravenous injection of midazolam (0.02 mg.kg(-1)) together with a 30-min propofol infusion designed to achieve an effect-site concentration of 1.0 μg.ml(-1). Observed variables included bispectral index, observer's assessment of...

Aims To evaluate the efficacy and safety of the PROMETATM Protocol for treating methamphetamine dependence. Design A double-blind, placebo-controlled 108-day study with random assignment to one of two study conditions: active medication with flumazenil (2 mg infusions on days 1, 2, 3, 22, 23), gabapentin (1200 mg to day 40) and hydroxazine (50 mg to day 10) versus placebo medication (with activ...

We used the benzodiazepine GABA(A) marker [(11)C] flumazenil to study cerebral dysfunction in amyotrophic lateral sclerosis (ALS) with PET. Seventeen non-demented patients with clinically definite or probable ALS were scanned and statistical parametric maps were derived to localize changes in regional flumazenil volumes of distribution (FMZVD), which correlate closely with receptor density (B(m...

Imidazo[1,5-a][1,4]benzodiazepines are well documented to exhibit potent activity at GABAA/Bz receptors. This series belongs to one of the very few chemical families, which have been extensively investigated for GABAA/Bz receptor mediated activity.1,2 Flumazenil (Ro 15-1788), an imidazo[1,5-a][1,4]benzodiazepine, was earlier shown to bind to central GABAA receptors with little or no intrinsic a...

The aim of the present experiment was to assess the involvement of adenosine receptor antagonists in benzodiazepine (BDZ) withdrawal signs, observed as the seizure susceptibility in mice. The discontinuation of chronic treatment with temazepam or diazepam decreased seizure threshold (one of BDZ withdrawal signs). The concomitant application of subconvulsive dose of pentetrazole (55.0 mg/kg) wit...