2-Acetyl-7-hydroxy-6-methoxy-1-methyl-1,2,3,4,-tetrahydroisoquinoline exhibits anti-inflammatory properties and protects the nigral dopaminergic neurons.
Eur J Pharmacol
; 771: 152-61, 2016 Jan 15.
Article
en En
| MEDLINE
| ID: mdl-26687634
ABSTRACT
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopamine(DA)ergic neurons. Neuroinflammation caused by microglial activation is believed to be involved in the pathogenesis of neurodegenerative diseases including PD. In the present study, we tested the effects of a novel compound 2-acetyl-7-hydroxy-6-methoxy-1-methyl-1,2,3,4,-tetarhydroisoquinoline (AMTIQ) on neuroinflammatory response and DAergic neurodegeneration. In lipopolysaccharide-activated BV-2 microglial cells, AMTIQ lowered nitric oxide and tetrahydrobiopterin levels and downregulated gene expression of inducible nitric oxide synthase and GTP cyclohydrolase I. AMTIQ also repressed gene expression of the proinflammatory cytokines IL-1ß and TNF-α, and attenuated nuclear translocation of NF-κB. AMTIQ was stable against liver microsomal enzymes from human and mouse and did not interfere with activities of the cytochrome p450 enzymes 1A2, 2D6, 2C9, 2C19 and 3A4. Pharmacokinetic studies revealed the brain to plasma ratio of AMTIQ to be 45%, suggesting it can penetrate the blood brain barrier. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse PD model, AMTIQ led to decreased microglial activation, increased survival of DAergic neurons and their fibers, and improved behavioral scores on rotarod and vertical grid tests. Taken together, these results suggest that AMTIQ might serve as a candidate preventive-therapeutic agent for neurodegenerative diseases such as PD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sustancia Negra
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Fármacos Neuroprotectores
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Neuronas Dopaminérgicas
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Isoquinolinas
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Antiinflamatorios
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Antiparkinsonianos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2016
Tipo del documento:
Article
País de afiliación:
Corea del Sur