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A polemic in response to Hermann et al. (Br. J. Clin. Pharmacol., 2012, 74, 203-4) is given. In their paper, Hermann et al. suggested that min. quality criteria are needed to communicate unexpected drug safety findings from randomized clin. trials and imply that the authors' previous report on unexpected frequent hepatotoxicity in patients receiving flupirtine for the treatment of overactive bladder syndrome does not meet such criteria. The authors argued that Hermann et al. suggested a faulty randomization or different baseline characteristics of the treatment groups as possible explanations for the observed hepatotoxicity in flupirtine-treated patients. They further disagree with the assessment by Hermann et al. that the decision to stop the study was flawed because it was based on 'single observations of liver test abnormalities' and a 'limited number of patients'. Addnl., the authors find Hermann et al.'s suggestion, that the switch from 400 to 600 mg daily flupirtine may have resulted in nonlinear kinetics with a threefold increase in exposure, misleading.

Screening of a pteridine-based compound library led to the identification of compounds exhibiting immunosuppressive as well as anti-inflammatory activity. Optimization afforded a series of 2-amino-4-N-piperazinyl-6-(3,4-dimethoxyphenyl)pteridine analogues. The most potent congeners in this series displayed low nM IC(50) values in the Mixed Lymphocyte Reaction (MLR) assay. In addition, these compounds also have potent anti-inflammatory activity as measured in the Tumor Necrosis Factor (TNF) assay.

A series of 3- and 5-aryl-1,2,4-oxadiazole derivatives were prepared and tested for anticonvulsant activity in a variety of models. These 1,2,4-oxadiazoles exhibit considerable activity in both pentylenetetrazole (PTZ) and maximal electroshock seizure (MES) models. Compound 10 was protective in the PTZ model in rats with an oral ED(50) of 25.5mg/kg and in the MES model in rats with an oral ED(50) of 14.6mg/kg. Neurotoxicity (rotarod) was observed with an ED(50) of 335mg/kg. We found several oxadiazoles that acted as selective GABA potentiating compounds with no interaction to the benzodiazepine binding site.