Linked Life Data

11394936

Source:http://linkedlifedata.com/resource/pubmed/id/11394936

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2001-6-7
pubmed:abstractText
The 1,4- and the 1,5-benzodiazepines (BDZ) are commonly used as anxiolytic and anticonvulsive drugs. It has been suggested that they influence, particularly through stimulation of peripheral BDZ receptors, some immune cell properties such as pro-inflammatory cytokine production. The availability of a new class of [1,2,4]triazolo[4,3-a][1,5]benzodiazepine derivatives (compounds IV), endowed with anti-inflammatory and/or analgesic properties but no anti-pentylenetetrazole activity, prompted us to investigate in more detail the anti-inflammatory properties of three selected compounds IV (N,N-dimethyl-1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benz- odiazepin-5-amine; N,N-dibutyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine; 1-methyl-N,N-dimethyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine) and one structurally related compound (1-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one). These BDZ derivatives have lost their affinity for the central and peripheral BDZ receptors. The in vivo effect on leukocyte migration of these compounds was investigated by using the mouse air-pouch model of local inflammation. Compounds A and B, significantly inhibited the carrageenan-induced leukocyte recruitment in a dose-dependent manner starting from the dose of 50 mgkg(-1), whereas compound C was effective only at the higher dose of 100 mgkg(-1). Compound D did not exert such effects at any of the doses considered. The effect of compounds A, B and C on leukocyte recruitment was paralleled by a significant inhibition of interleukin-6 and prostaglandin E(2)production in the exudate, similarly to indomethacin, and by a partial reduction of vascular permeability. These features may be relevant for the design and development of innovative anti-inflammatory molecules among the 4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amine derivatives.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1043-6618
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-52
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
1,5-Benzodiazepine tricyclic derivatives exerting anti-inflammatory effects in mice by inhibiting interleukin-6 and prostaglandinE(2)production.
pubmed:affiliation
Department of Molecular Biochemistry and Pharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy.
pubmed:publicationType
Journal Article