abcb1ab p-glycoprotein is involved in the uptake of the novel antidepressant vortioxetine into the brain of mice.
J Psychiatr Res
; 109: 48-51, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30476727
ABSTRACT
A clinically important and well-studied transporter of the blood-brain barrier (BBB) is P-glycoprotein (P-gp), the gene product of ABCB1. Animal studies have shown that brain concentrations of many antidepressants depend on P-gp. However, biochemical properties, which might allow the prediction of pharmacodynamical involvement of P-gp have not yet been identified, hence thorough experimental testing of each novel drug is needed to determine its P-gp substrate status. In the current study, we tested the P-gp substrate status for the antidepressant vortioxetine using double abcb1ab knock-out (KO) mice. Cerebral concentrations of vortioxetine were 2.3 times higher in P-gp deficient mice compared to wildtype (WT) controls. No significant difference was found regarding the concentration of the drug in the plasma and other organs (liver, kidney, spleen) between KO and WT mice. The results of our study provide conclusive in-vivo evidence that in mice vortioxetine's brain bioavailability is P-gp dependent, expanding previous findings on this topic.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Encéfalo
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Barrera Hematoencefálica
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
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Vortioxetina
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Antidepresivos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Psychiatr Res
Año:
2019
Tipo del documento:
Article