Regional increase in P-glycoprotein function in the blood-brain barrier of patients with chronic schizophrenia: a PET study with [(11)C]verapamil as a probe for P-glycoprotein function.
Psychiatry Res
; 183(2): 151-6, 2010 Aug 30.
Article
em En
| MEDLINE
| ID: mdl-20620031
ABSTRACT
P-glycoprotein (P-gp), a major efflux pump in the blood-brain barrier (BBB) has a profound effect on entry of drugs, peptides and other substances into the central nervous system (CNS). The brain's permeability can be negatively influenced by modulation of the transport function of P-gp. Inflammatory mediators play a role in schizophrenia, and may be able to influence the integrity of the BBB, via P-gp modulation. We hypothesized that P-gp function in the BBB is changed in patients with schizophrenia. Positron-emission tomography was used to measure brain uptake of [(11)C]verapamil, which is normally extruded from the brain by P-gp. We found that patients with chronic schizophrenia under treatment with antipsychotic drugs compared with healthy controls showed a significant decrease in [(11)C]verapamil uptake in the temporal cortex, the basal ganglia, and the amygdala, and amygdalae, and a trend towards a significant decrease was seen throughout the brain. The decrease of [(11)C]verapamil uptake correlates with an increased activity of the P-gp pump. Increased P-gp activity may be a factor in drug resistance in schizophrenia, induced by the use of antipsychotic agents.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
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Mapeamento Encefálico
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Barreira Hematoencefálica
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Psychiatry Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Holanda