Synthesis and Evaluation of a Redox Chemical Delivery System for Brain-Enhanced Dopamine Containing an Activated Carbamate-Type Ester
作者:
OmarF. A.,
FaragH. H.,
BodorN.,
期刊:
Journal of Drug Targeting
(Taylor Available online 1994)
卷期:
Volume 2,
issue 4
页码: 309-316
ISSN:1061-186X
年代: 1994
DOI:10.3109/10611869409015911
出版商: Taylor&Francis
关键词: Dopamine;activated carbamate esters;chemical delivery system;brain delivery
数据来源: Taylor
摘要:
AbstractA chemical delivery system (CDS) for enhanced delivery of dopamine to brain tissue, based on a dihydropyridine⟺pyridinium salt redox system, was modified to include an activated carbamate ester. The dihydronicotinate moiety was chemically attached to the amino group of dopamine (DA) by acylation with chloroethyl chloroformate, followed by condensation with sodium nicotinate under mild conditions. The product was selectively N-alkylated at the pyridine ring and subjected to regioselective reduction to the corresponding 1,4-dihydropyridine derivative, DA-CDSac.In vitrostability of the new compound was studied in phosphate buffers at mild acidic, physiological, and mild alkaline pH values. Oxidation studies showed facile conversion of the dihydronicotinate, DA-CDSac, is readily converted to the corresponding quaternary salt, both chemically and enzymatically.In vivostudies in rats did not detect sustained increases in brain levels of the quaternary salt after i.v. dosing with DA-CDSac. However, the new CDS appeared to change spontaneous locomotor activity in rats after i.v. administration which may be due to altered central DA neuronal activity.
点击下载:
PDF (623KB)
返 回