A5055973215- Sleep and Wakefulness Research
- Sleep and related disorders
- Neuroscience and Neuropharmacology Research
- Circadian rhythm and melatonin
- Tryptophan and brain disorders
- Neural dynamics and brain function
- Amino Acid Enzymes and Metabolism
- Sleep and Work-Related Fatigue
- Photochromic and Fluorescence Chemistry
- Neurogenesis and neuroplasticity mechanisms
- Drug Transport and Resistance Mechanisms
- Heart Rate Variability and Autonomic Control
- Neuroscience and Neural Engineering
- Biochemical Analysis and Sensing Techniques
- Memory and Neural Mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Receptor Mechanisms and Signaling
Taisho Pharmaceutical (Japan)
2010-2023
Weatherford College
2020
Tokyo Medical and Dental University
2010
Abstract Rationale Novel compound with potent antagonistic activity against orexin receptors may be new treatment option for patients insomnia. Objective The aim was to investigate the efficacy and safety of single oral doses dual receptor antagonist TS-142 in Methods This multicenter, double-blind, crossover randomized clinical trial included non-elderly Patients were receive placebo at 5, 10, 30 mg one four different sequences, a 7-day washout period between treatments. Primary endpoints...
Abstract The pharmacokinetics, pharmacodynamics and safety profile of vornorexant were investigated in healthy Japanese participants three double‐blind studies: a single ascending dose 1–30 mg (Study 101; n = 6) multiple doses 10–30 102; 6). Study 202 consisted two steps: an open‐label, 20 repeated‐dose non‐elderly individuals (Step 1; 12) double‐blind, elderly 2; 8/3 for vornorexant/placebo). Vornorexant was rapidly absorbed eliminated under fasting conditions, with time to maximum plasma...
We previously identified 3-chloro-N-{(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidine-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (5, TP0439150) as a potent and orally available glycine transporter 1 (GlyT1) inhibitor. In this article, we describe our identification of 1-methyl-N-(propan-2-yl)-N-({2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1H-imidazole-4-carboxamide (7n) structurally diverse back-up compound 5, using central nervous system multiparameter...
Abstract Introduction: Drugs acting on the central nervous system (CNS), especially hypnotics, can impair driving. The US Food and Drug Administration started requiring pharmaceutical companies to evaluate residual influence of CNS agents driving performance review their recommended doses. Although it is important for physicians discuss automobile while medication with patients promote traffic safety, package inserts most in Japan uniformly prohibit from more evidence-based information...
Abstract Introduction TS-142 is a novel dual orexin receptor antagonist (DORA) developed for the treatment of insomnia. Here we report its pharmacokinetic profile in healthy subjects and efficacy safety patients with Methods A phase1 study was conducted to clarify profile, which various doses (1–30 mg) were orally administered once thirty two subjects. Subsequently, phase 2a utilizing polysomnography (PSG) carried out primary insomnia, 5, 10, or 30 mg TS-142, placebo randomly double-blind...
Abstract Introduction The orexin system plays a pivotal role in regulating sleep and wakefulness, thus, receptors (OX1 OX2 receptors) have gained much attention as promising therapeutic targets for the treatment of insomnia. We synthesized novel potent dual receptor antagonist (DORA), ORN0829 (investigation code name TS-142), which was designed to short-acting effects. Here we report pharmacological pharmacokinetic profiles rats. Methods antagonistic activities were assessed using calcium...