(J Vase Surg 2012;55:24-32.)”
“Benzodiazepines (BZs) are effective anxiolytics and hypnotics, but their use is limited by unwanted side effects, such as motor impairment.

To assess the contribution of alpha 1 subunit-containing gamma-aminobutyric acid(A) (GABA(A)) receptor subtypes to the motor-impairing effects of BZs, the present study evaluated two observable measures of motor coordination (balance on a pole, resistance to hind-limb flexion) engendered by nonselective and selective BZ-site agonists in squirrel monkeys.

Multiple doses of nonselective

BZs (triazolam, alprazolam, diazepam, and chlordiazepoxide) and alpha 1 subunit-preferring agonists (zolpidem and zaleplon) were administered to adult male squirrel monkeys (N = 4-6), and experimenters rated the monkey’s ability to balance on a horizontal pole (“”ataxic-like effects”"), as well as the degree of BI 2536 molecular weight resistance to hind-limb flexion (“”myorelaxant-like Navitoclax in vivo effects”").

Administration of all BZ-type drugs resulted in ataxic-like and myorelaxant-like effects. Pretreatment with the alpha 1 subunit-preferring antagonist beta-carboline-3-carboxylate-t-butyl ester (beta CCT) attenuated the ataxic-like effects engendered by both types of drugs. However, beta CCT was largely ineffective at blocking the ability of both BZs and non-BZs to induce myorelaxant-like effects.

These experiments demonstrate dose-dependent motor impairment

in squirrel monkeys using quantitative behavioral observation techniques. Altogether, these findings suggest a lack of a prominent role for alpha 1 subunit-containing receptors in the alteration of hind-limb flexion, a putative measure of myorelaxation, induced by BZ-type drugs in monkeys.”
“In

the mammalian CNS, excessive release of glutamate and overactivation of glutamate receptors are responsible for the Tucidinostat clinical trial secondary (delayed) neuronal death following neuronal injury, including ischemia, traumatic brain injury (TBI) and epilepsy. Recent studies in mice showed a critical role for neuronal gap junctions in NMDA receptor-mediated excitotoxicity and ischemia-mediated neuronal death. Here, using controlled cortical impact (CCI) in adult mice, as a model of TBI, and Fluoro-jade B staining for analysis of neuronal death, we set to determine whether neuronal gap junctions play a role in the CCI-mediated secondary neuronal death. We report that 24 h post-CCI, substantial neuronal death is detected in a number of brain regions outside the injury core, including the striatum. The striatal neuronal death is reduced both in wild-type mice by systemic administration of mefloquine (a relatively selective blocker of neuronal gap junctions) and in knockout mice lacking connexin 36 (neuronal gap junction protein). It is also reduced by inactivation of group II metabotropic glutamate receptors (with LY341495) which, as reported previously, control the rapid increase in neuronal gap junction coupling following different types of neuronal injury.