학술논문
Pyridazinoquinolinetriones as NMDA Glycine-Site Antagonists with Oral Antinociceptive Activity in a Model of Neuropathic Pain.
Document Type
Article
Author
Thomas M. Bare; Dean G. Brown; Carey L. Horchler; Megan Murphy; Rebecca A. Urbanek; Vernon Alford; Christine Barlaam; Martin C. Dyroff; James B. Empfield; Janet M. Forst; Keith J. Herzog; Richard A. Keith; Alan S. Kirschner; Chi-Ming C. Lee; Joseph Lewis; Frances M. McLaren; Kathy L. Neilson; Gary B. Steelman; Shephali Trivedi; Edward P. Vacek
Source
Subject
*GLYCINE
*CHEMICAL inhibitors
*BIOAVAILABILITY
*PAIN
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*
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Language
ISSN
0022-2623
Abstract
A series of 7-chloro-2,3-dihydro-2-1-(pyridinyl)alkyl-pyridazino4,5-bquinoline-1,4,10(5H)-triones were synthesized and found to have potent activity at the glycine site of the NMDA receptor. In some cases, these compounds possessed poor aqueous solubility that may have contributed to poor rat oral bioavailability. Subsequently, compounds have been identified with improved aqueous solubility and oral bioavailability. Several of these compounds were examined in a rat chronic constrictive injury (CCI) model of neuropathic pain and found to have potent activity when dosed orally. [ABSTRACT FROM AUTHOR]