A PDE10A inhibitor CPL500036 is a novel agent modulating striatal function devoid of most neuroleptic side-effects.

Phosphodiesterase 10A (PDE10A) is expressed almost exclusively in the striatum and its inhibition is suggested to offer potential treatment in disorders associated with basal ganglia. We evaluated the selectivity, cytotoxicity, genotoxicity, pharmacokinetics and potential adverse effects of a novel PDE10A inhibitor, CPL500036, . The potency of CPL500036 was demonstrated by microfluidic technology, and selectivity was investigated in a radioligand binding assay against 44 targets.

P-Glycoprotein Inhibitor Tariquidar Plays an Important Regulatory Role in Pigmentation in Larval Zebrafish.

Zebrafish has emerged as a powerful model in studies dealing with pigment development and pathobiology of pigment diseases. Due to its conserved pigment pattern with established genetic background, the zebrafish is used for screening of active compounds influencing melanophore, iridophore, and xanthophore development and differentiation. In our study, zebrafish embryos and larvae were used to investigate the influence of third-generation noncompetitive P-glycoprotein inhibitor, tariquidar (TQR), on pigmentation, including phenotype effects and changes in gene expression of chosen chromatophore differentiation markers.

Percutaneous Occlusion of the Left Atrial Appendage with Thrombus Irresponsive to Antithrombotic Therapy.

We analyzed clinical experience with percutaneous closure of instances of left atrial appendage with thrombus (LAAT) irresponsive to antithrombotic therapy in patients treated in three high-volume cardiology centers. Clinical and procedural data regarding consecutive patients who underwent percutaneous left atrial appendage closure (PLAAC) due to LAAT were retrospectively analyzed. The study population consisted of 17 patients (11 men; 68 ± 14 years; CHADSVASC 4.

Association of p75(NTR) and α9β1 integrin modulates NGF-dependent cellular responses.

Direct interaction of α9β1 integrin with nerve growth factor (NGF) has been previously reported to induce pro-proliferative and pro-survival activities of non-neuronal cells. We investigated participation of p75(NTR) in α9β1 integrin-dependent cellular response to NGF stimulation. Using selective transfection of glioma cell lines with these receptors, we showed a strong, cation-independent association of α9 integrin subunit with p75(NTR) on the cellular membrane by selective immunoprecipitation experiments.

Identification of inhibitors of α2β1 integrin, members of C-lectin type proteins, in Echis sochureki venom.

Snake venom antagonists of α2β1 integrin have been identified as members of a C-lectin type family of proteins (CLP). In the present study, we characterized three new CLPs isolated from Echis sochureki venom, which interact with this integrin. These proteins were purified using a combination of gel filtration, ion exchange chromatography and reverse phase HPLC.

Residual fraction of the area under the curve as a qualitative criterion in pharmacokinetic studies.

The aim of the present study was to determine whether the residual area under the curve (AUC(res%); expressed as % of total value of AUC) could be used as a parameter for the qualitative evaluation of pharmacokinetic studies.We propose new criteria for the qualitative evaluation of pharmacokinetic analysis. Two sets of hypothetical data that illustrate the relationship between concentration and time were used for the analysis of drug pharmacokinetics.