Activation of indirect pathway medium spiny neurons (MSNs) via promotion of cAMP production is the principal mechanism of action of current antipsychotics with dopamine D2 receptor antagonism. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a novel phosphodiesterase 10A inhibitor that activates both direct and indirect pathway MSNs t...

Cognitive deficits in various domains, including recognition memory, attention, impulsivity, working memory, and executive function, substantially affect functional outcomes in patients with schizophrenia. TAK-063 [1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one] is a potent and selective phosphodiesterase 10A inhibitor that produces antipsychoti...

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...

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...

접수일:2009년 2월 12일, 승인일:2009년 4월 1일 책임저자:이 철, (570-749) 전북 익산시 신용동 344-2 원광대학교 의과대학 마취통증의학교실 Tel: 063-859-1560, Fax: 063-857-5472 E-mail: [email protected] 2009년도 원광대학교 교내연구비 지원에 의함. Received February 12, 2009, Accepted April 1, 2009 Correspondence to: Cheol Lee Department of Anesthesiology and Pain Medicine, School of Medicine, Wonkwang University, 344-2, Sinyong-dong, Iksan 570-749, Korea ...