In vitro metabolic studies on the selective metabotropic glutamate receptor sub-type 5 (mGluR5) antagonist 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl]-pyridine (MTEP).
Neurosci Lett
; 391(3): 91-5, 2006 Jan 02.
Article
em En
| MEDLINE
| ID: mdl-16153770
ABSTRACT
Metabotropic glutamate receptors (mGluR) are G-protein-coupled receptors that play a major role in modulatory pathways in the CNS and have been suggested to have pharmacological implications in pain, psychiatric disorders and other neurological states. 3-[(2-Methyl-1,3-thiazol-4-yl) ethynyl]-pyridine (MTEP) is a specific and selective antagonist for the mGluR sub-type 5. Previous studies using rat liver microsomes showed that the major oxidative metabolites of MTEP are a hydroxymethyl metabolite (M1), two oxides (M2 and M4), a thiazole-ring opened metabolite (M3) and CO(2) (M5). In the present study, we examined the metabolism of MTEP in liver microsomes and expressed rat and human CYP isoforms. In rat liver microsomes, metabolic stability studies accurately predicted the in vivo clearance for MTEP. Incubation of MTEP with expressed rat and human CYP isoforms showed that CYP1A and CYP2C isoforms are primarily responsible for the metabolism of this compound. The results suggest that species differences in MTEP metabolism is possible and could contribute to specie-differences in biological effects of the compound.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piridinas
/
Tiazóis
/
Microssomos Hepáticos
/
Receptores de Glutamato Metabotrópico
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos