Prodromal dysfunction of α5GABA-A receptor modulated hippocampal ripples occurs prior to neurodegeneration in the TgF344-AD rat model of Alzheimer's disease.

Decades of research attempting to slow the onset of Alzheimer's disease (AD) indicates that a better understanding of memory will be key to the discovery of effective therapeutic approaches. Here, we ask whether prodromal neural network dysfunction might occur in the hippocampal trisynaptic circuit by using α5IA (an established memory enhancer and selective negative allosteric modulator of extrasynaptic tonically active α5GABA-A receptors) as a probe drug in TgF344-AD transgenic rats, a model for β-amyloid induced early onset AD. The results demonstrate that orally bioavailable α5IA increases CA1 pyramidal cell mean firing rates during foraging and peak ripple amplitude during wakeful immobility in F344 rats in a familiar environment.

Pharmacological Properties of DOV 315,090, an ocinaplon metabolite.

Background: Compounds targeting the benzodiazepine binding site of the GABAA-R are widely prescribed for the treatment of anxiety disorders, epilepsy, and insomnia as well as for pre-anesthetic sedation and muscle relaxation. It has been hypothesized that these various pharmacological effects are mediated by different GABAA-R subtypes. If this hypothesis is correct, then it may be possible to develop compounds targeting particular GABAA-R subtypes as, for example, selective anxiolytics with a diminished side effect profile.

Benzodiazepine modulation of partial agonist efficacy and spontaneously active GABA(A) receptors supports an allosteric model of modulation.

Benzodiazepines (BZDs) have been used extensively for more than 40 years because of their high therapeutic index and low toxicity. Although BZDs are understood to act primarily as allosteric modulators of GABA(A) receptors, the mechanism of modulation is not well understood. The applicability of an allosteric model with two binding sites for gamma-aminobutyric acid (GABA) and one for a BZD-like modulator was investigated.

Excellence in supply chain management--trends and strategies to enhance profitability. Panel discussion.

Supply-chain management--the art of getting the most at the least cost from the products and services purchased by an organization--has transformed industries such as manufacturing and retailing, and can potentially do the same for healthcare. VHA is committed to keeping its members educated on current thinking and best practices in supply-chain management. In support of that mission, four supply chain experts gathered in Chicago recently at Modern Healthcare's offices to discuss the issues they face in their organizations and the strategies they've found most successful in addressing them.