A5085011117- Neuroscience and Neuropharmacology Research
- Tryptophan and brain disorders
- Amino Acid Enzymes and Metabolism
- Drug Transport and Resistance Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Treatment of Major Depression
- Receptor Mechanisms and Signaling
- Plant-based Medicinal Research
- Cholinesterase and Neurodegenerative Diseases
- Biochemical effects in animals
- Pharmacological Receptor Mechanisms and Effects
- Metabolism and Genetic Disorders
- Eicosanoids and Hypertension Pharmacology
- Diabetes Treatment and Management
- Crystallography and molecular interactions
- Analytical Methods in Pharmaceuticals
- Pharmacogenetics and Drug Metabolism
- Phosphodiesterase function and regulation
- Connexins and lens biology
- Gastrointestinal motility and disorders
- Enzyme Structure and Function
- Analytical Chemistry and Chromatography
- Biochemical Analysis and Sensing Techniques
Taisho Pharmaceutical (Japan)
2012-2023
TP0473292 (the active ingredient of TS-161) is a prodrug novel metabotropic glutamate (mGlu) 2/3 receptor antagonist being developed for the treatment patients with depression. This study evaluated safety, tolerability, and pharmacokinetics orally administered TS-161 in healthy subjects.This was first-in-human, phase 1, randomized, double-blind, placebo-controlled, single-ascending dose (15-400 mg 10-day multiple-ascending (50-150 subjects, conducted from June 2019 through February 2020....
Abstract MGS0274 besylate is an ester‐based lipophilic prodrug of a metabotropic glutamate (mGlu) 2 and mGlu3 receptor agonist MGS0008 being developed for the treatment schizophrenia. We investigated disposition these compounds in rats monkeys vitro metabolism humans to evaluate whether could be useful as humans. After oral administration (2.89 mg/kg), was immediately found plasma, reached maximum concentration at 4 hours postdose, decreased with terminal half‐life 16.7 hours; barely...
The safety and pharmacokinetics of single multiple doses a novel mGlu2/3 receptor agonist prodrug, MGS0274 besylate (TS-134), were investigated in healthy subjects.Phase 1 single-ascending dose (5-20 mg) multiple-ascending titration (5-80 studies conducted male female subjects. Both randomized, double-blinded placebo-controlled. In one cohort study (10 mg), concentrations MGS0008, the active compound, cerebrospinal fluid (CSF) measured for up to 24 hours postdose.Following oral...
TP0473292 is an adamantane carboxylic acid (ACA) ester prodrug for enhancing the oral bioavailability of hydrophilic glutamate analog TP0178894, a novel metabotropic 2 and 3 receptor antagonist, being developed as antidepressant. showed high membrane permeability rapid hydrolysis to TP0178894 in rat, monkey, human liver S9 fractions, with conversion rate such that complete by first-pass metabolism was expected. also hydrolyzed intestinal, renal, lung coinciding result activated...
A strategy for assessing potential drug-drug interactions (DDIs) based on a simulated intestinal concentration is described. The proposed prediction method was applied to the DDI assessment of luseogliflozin, novel antidiabetic drug, against miglitol absorbed via sodium-glucose cotransporter 1 (SGLT1). involves four steps: collection physicochemical and pharmacokinetic parameters luseogliflozin use in computer simulation; evaluation validity these by verifying goodness fit between observed...
A sensitive, selective and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of miglitol in rat plasma. The sample preparation procedures involved protein precipitation unique solid-phase extraction, which efficiently removed sources ion suppression column degradation interference present Chromatographic separation achieved on an amide using 10 mmol/L CH3 COONH4 CN:CH3 OH (90:10, v/v) as mobile phase under gradient conditions....
For ester prodrugs that are used to improve the gastrointestinal absorption of highly hydrophilic, pharmacologically active substances, it is challenging predict human pharmacokinetics (PK) and their parent compounds using only preclinical data.This research was aimed at constructing a PBPK model for predicting PK prodrug MGS0274 its compound MGS0008 after single oral administration besylate.First, we identified carboxylesterase 1 (CES1) as major enzyme involved in hydrolysis MGS0274....
TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study dogs. Histopathologically, the observed degeneration of lens fibers, characterized by irregularity ordered arrangement fibers which is necessary maintain transparency lens, and considered manifest clinically cataract. To evaluate development mechanism opacity, chemical constituents known be associated with cataract, were examined. The results liquid chromatography-tandem...