INTRODUCTION Over the past decade, drug companies have focused much of their attention on addressing the problem of insomnia. This effort should come as no surprise— insomnia is being reported at an alarmingly high rate. In 2005, the National Sleep Foundation, part of the National Institutes of Health, estimated that more than half (54%) of all Americans were reporting symptoms of insomnia a fe...

BACKGROUND Benzodiazepines (BZD) are the most widely used sedative-hypnotics, and evidence is rapidly accumulating suggesting potential BZD dependence, association of chronic use with adverse effects and a definite abstinence syndrome produced by withdrawal. AIMS The present investigation followed prospectively long-term BZD users over 1 year following graded BZD withdrawal in terms of clinic...

This study investigated factors associated with long-term use of benzodiazepines (BZDs) or benzodiazepine receptor agonists (BzRAs) as hypnotics in patients with chronic insomnia. Consecutive patients (n = 140) with chronic insomnia were enrolled in this study (68 men and 72 women; mean age, 53.8 ± 10.8 years). All patients filled out a self-assessment questionnaire asking clinical descriptive ...

Benzodiazepines (BZDs) exert their effects in the CNS by binding to a modulatory site on GABA(A) receptors. Individual amino acids have been implicated in BZD recognition and modulation of the GABA(A) receptor, but the secondary structure of the amino acids contributing to the BZD binding site has not been elucidated. In this report we used the substituted cysteine accessibility method to under...

The mechanisms by which the GABA and benzodiazepine (BZD) binding sites of the GABA-A receptor are allosterically coupled remain elusive. In this study, we separately monitored ligand-induced structural changes in the BZD binding site (alpha/gamma interface) and at aligned positions in the alpha/beta interface. alpha(1)His101 and surrounding residues were individually mutated to cysteine and ex...

CONTEXT Hypotension is one of the dose limiting side effects of benzodiazepines (BZDs), in particular of diazepam (DZP) which is still widely used in the clinic. Currently, only one FDA approved antidote exists for BZD overdose and novel approaches are needed to improve management of DZP overdose, dependency and withdrawal. OBJECTIVE Here, we hypothesized that increasing bioactive lipid media...

Many clinically important drugs target ligand-gated ion channels; however, the mechanisms by which these drugs modulate channel function remain elusive. Benzodiazepines (BZDs), anesthetics, and barbiturates exert their CNS actions by binding to GABA(A) receptors and modulating their function. The structural mechanisms by which BZD binding is transduced to potentiation or inhibition of GABA-indu...

Clinical and experimental studies suggest possible risks associated with the repeated administration of benzodiazepines (BZDs) during the prenatal or early postnatal period on further development and behavior. In the present study, we assess short- and long-term effects of early exposure to clonazepam (CZP) on cognitive tasks. CZP (0.5 or 1.0 mg/kg/day) was administered from postnatal day (P)7 ...

BACKGROUND Opioid-substitution treatment (OST) for opioid dependence (OD) has proven effective in retaining patients in treatment and reducing illegal opiate abuse and crime. Consequently, the World Health Organization (WHO) has listed the opioid agonists methadone and buprenorphine as essential drugs for OD that should be available worldwide. In many areas of the world, OD is often associated ...

Several agents are known to improve sleep induction and/or maintenance in patients with insomnia disorder. These include the benzodiazepine (BZD) and non-BZD receptor allosteric modulators, the melatonin receptor agonist ramelteon, low-dose doxepin, and suvorexant. One of the drawbacks of the BZDs is their known reduction in both N3 sleep [also known as slow wave sleep or delta sleep and charac...