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NXY-059 (disufenton sodium) is a novel, free-radical-trapping neuroprotectant, which, until recently, was in clinical development for the treatment of acute ischemic stroke based on effects seen in experimental animal models. [...]

NXY-059 is a novel free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a [...]

NXY-059 is a free radical-trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. Acute ischemic stroke patients receiving NXY-059 may also be [...]

Objective: To investigate the intragastric acid neutralization activity of a combined alginate-antacid formulation. Significance: Published studies have investigated the reflux-suppressing alginate component of Gaviscon Double Action (Gaviscon DA; RB, UK) but intragastric acid neutralization activity of the antacid component has not been evaluated in vivo. Methods: Intragastric pH monitoring, using a custom-made 10-electrode catheter, was evaluated in a two-part exploratory study in healthy subjects; Part I (n = 6) tested suitability of the catheter using antacid tablets (Rennie; Bayer, Germany); Part II (n = 12) evaluated gastric acid neutralization activity of Gaviscon DA liquid (20 ml) versus placebo in fasted subjects using a randomized, open-label, crossover design. The primary endpoint was the percentage of time that intragastric pH ≥4 was measured during 30 min post-treatment. A confirmatory study of identical design was subsequently conducted (n = 20). Results: Monitoring pH using the multielectrode catheter was a viable approach, directly detecting changes in intragastric pH following a single dose of antacid tablets. In the exploratory study, the percentage of time that pH ≥4 during 30 minutes post-treatment was 46.8% with Gaviscon DA liquid versus 4.7% with placebo (p = 0.0004). These findings were supported by the confirmatory study, where pH ≥4 was recorded 50.8% of the time with Gaviscon DA versus 3.5% with placebo (p = 0.0051). In this study, Gaviscon DA was safe and well tolerated. Conclusions: These studies demonstrate the effective acid neutralizing capacity of Gaviscon DA versus placebo in healthy, fasted subjects. This adds to the evidence base for the combination of alginates and antacids. [ABSTRACT FROM AUTHOR]

Background/aim: Timed interval cerebrospinal fluid (CSF) sampling by indwelling catheterization can be a valuable corroborative tool for the pharmacokinetic and pharmacodynamic assessment of drugs. CSF sampling in studies on drug candidates for Alzheimer's disease have been conducted in evaluations of the biomarkers acetylcholine (ACh), tau proteins, amyloid precursor protein and beta-amyloid fragments. The primary aim of this study was to study the feasibility and the burden on the healthy volunteers of serial CSF sampling within the contract research organization environment in order to establish a standardized research tool for future drug development studies. Materials and methods: This study is a validation study in healthy subjects: eight healthy male subjects aged 55-75 years were enrolled. After eligibility had been confirmed, the subjects were admitted to the clinical pharmacology unit 2 days before starting the CSF sampling procedure. Hydration by drip infusion of 2 L saline was performed for 24 h before starting the CSF sampling procedure, and for antithrombotic purposes, Fraxiparine (nadroparine calcium) was given 12 and 36 h after intradural catheterization. CSF catheterization was performed by board-certified anesthesiologists with experience in inserting indwelling intrathecal catheters. Subjects only required to remain in a horizontal position for the first 24 h after removal of the catheter. CSF and blood samples were collected by interval sampling over a 30-h period. Results: The study was completed by seven of the eight subjects. Six subjects who completed the study reported adverse effects (AEs) which were all mild and from which they recovered during their stay in the clinic. A total of 25 AEs were reported of which 13 were considered to be procedure-related. The procedure was well tolerated by all participating subjects, and the VAS scale scores for headache and back pain were low. CSF samples were analyzed for ACh. All values were above the lowest limit of quantification. On average, the ACh concentration started at a low level but rose between 1 and 2 h after insertion of the catheter and then remained high during the whole sampling period up to 30 h. Conclusion: Serial sampling of CSF in seven healthy volunteers up to 30 h occurred without serious complications and was well tolerated. The CSF collected was of good quality and facilitated the assessment of an Alzheimer's disease-sensitive biomarker. We conclude that this validation study can form the basis for future patient studies aimed at elucidating disease mechanisms and the pharmacodynamics of drugs in the developmental stage. [ABSTRACT FROM AUTHOR]

The article discusses a study which highlighted that healthy subjects receiving intravenous (iv) infusions of novel neuroprotectant (NXY-059) is mainly eliminated unchanged by renal excretion. It discusses whether NXY-059 uses the active secretory pathway for acids or bases, using inhibitors of these pathways, probenecid and cimetidine, respectively.

Evaluates the use of mephenytoin as a probe for CYP2C19 phenotyping. Urinary (S)-mephenytoin to (R)-mephenytoin ratio; Risk of incorrect classification; Intraindividual reproducibility of the ratio.

Possible ionic mechanisms by which activation of presynaptic α-adrenoceptors might inhibit the K-induced release of H-noradrenaline from superfused rat cerebral cortex slices or synaptosomes were investigated. The data indicate that Na, K and Cl movements across the neuronal membrane are involved in the K-induced release of H-noradrenaline from brain slices and synaptosomes. However, inhibition of K-induced H-noradrenaline release by activation of presynaptic α-receptors is probably not mediated by changes in the permeabilities for either Na, K or Cl. The results of this study emphasize the pivotal role of Ca in the presynaptic α-adrenergic modulation of noradrenaline release. [ABSTRACT FROM AUTHOR]