Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. We evaluated the in vivo pharmacological profile of a potent and selective PDE10A inhibitor, TAK-063 (1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-pyridazin-4(1H)-one). TAK-063 at 0.3 and 1 mg/kg p.o., increased cAMP and cGMP levels in...

Phosphodiesterase 10A (PDE10A) is a cAMP/cGMP phosphodiesterase highly expressed in medium spiny neurons (MSNs) in the striatum. We evaluated the in vivo pharmacological profile of a potent and selective PDE10A inhibitor, TAK-063 (1-[2-fluoro-4(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one). TAK-063 at 0.3 and 1 mg/kg p.o., increased cAMP and cGMP levels in t...

BACKGROUND Phosphodiesterase 10A (PDE10A) is selectively expressed in medium spiny neurons of the striatum. TAK-063 is a selective inhibitor of PDE10A in clinical development for the treatment of schizophrenia. OBJECTIVES Safety, tolerability, and pharmacokinetics (PK) of TAK-063 were evaluated following multiple rising oral doses, and PK/adverse event (AE) models were developed to characteri...

Phosphodiesterase 10A (PDE10A) inhibition is a novel and promising approach for the treatment of central nervous system disorders such as schizophrenia and Huntington's disease. A novel PDE10A inhibitor, TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)-pyridazin-4(1H)-one] has shown high inhibitory activity and selectivity for human recombinant PDE10A2 in v...

tality in industrialized societies. However, a significant part of the variation of the incidence of atherosclerosis diseases is not explained by its recognized risk factors. To enhance understanding of and to be able to prevent the atherosclerotic process, additional risk markers need to be identified. Sialic acid comprises a family of acylated derivates of neuraminic acid. It is widely distri...

Abstract. Identifying the associations between health and personality has been a focus for psychophysiological research. Type D is associated with predisposition to physical psychological ill-health. This statistician-blind parallel-group controlled trial (intervention group vs. waiting list control group) examined impact of Havening Techniques on constituents negative affect (NA) social inhibi...

Serum lipids, lipids (cholesterol, triglycerides and phospholipids) and apo-A in d.>1. 063 fraction, HDL2, HDL8 and VHDL of 10 normal subjects and 34 patients with chronic liver diseases (chronic aggressive hepatitis 2A and 2B, and liver cirrhosis in the compensated and decompensated stages) were analyzed. The analysis of d.>1. 063 and its subfractions (HDL2, HDL8 and VHDL) was achieved by rela...

Предлагаются методологические основы проектирования инструментального комплекса онтологического назначения, предназначенного для реализации интегрированной информационной технологии автоматизированного построения онтологий предметных областей. Полученные результаты ориентированы на повышение эффективности анализа и понимания естественноязыковых текстов, построения баз знаний предметных областей...