Safety and pharmacokinetic profiles of MGS0274 besylate (TS-134), a novel metabotropic glutamate 2/3 receptor agonist prodrug, in healthy subjects.
MGS0008
MGS0274
TS-134
cerebrospinal fluid
mGlu2/3 agonist
schizophrenia
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
11
02
2020
revised:
30
03
2020
accepted:
20
04
2020
pubmed:
1
5
2020
medline:
29
7
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
The safety and pharmacokinetics of single and multiple doses of a novel mGlu Phase 1 single-ascending dose (5-20 mg) and multiple-ascending dose titration (5-80 mg) studies were conducted in healthy male and female subjects. Both studies were randomized, double-blinded and placebo-controlled. In one cohort of single-ascending dose study (10 mg), concentrations of MGS0008, the active compound, in the cerebrospinal fluid (CSF) were measured for up to 24 hours postdose. Following single and multiple oral administrations, MGS0274 was rapidly absorbed and extensively converted into MGS0008, which reached a maximum concentration (C TS-134 is orally bioavailable in humans and converts rapidly and extensively to MGS0008, which exhibits good CSF penetration. Orally administered TS-134 was safe and generally well-tolerated; hence, TS-134 is a promising candidate for further clinical development for the treatment of disorders in which glutamatergic abnormalities are involved, such as schizophrenia.
Identifiants
pubmed: 32353162
doi: 10.1111/bcp.14331
pmc: PMC7576618
doi:
Substances chimiques
Glutamates
0
Prodrugs
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2286-2301Subventions
Organisme : Taisho Pharmaceutical Co., Ltd.
Organisme : Taisho Pharmaceutical R&D Inc.
Informations de copyright
© 2020 Taisho Pharmaceutical R&D Inc. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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