Linked Life Data

10602708

Source:http://linkedlifedata.com/resource/pubmed/id/10602708

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
25
pubmed:dateCreated
2000-1-24
pubmed:abstractText
Analogues of nonsteroidal antiinflammatory drugs (NSAIDs) oxicams, in which the active group was linked to a quaternary ammonium function [(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)2-methylpyridinium iodide or piroxicam-N(+) and [3-(4-hydroxy-2-methyl-2H-1,2-benzothiazine-1, 1-dioxide-3-carboxamido)propyl]trimethylammonium iodide or propoxicam-N(+)] were synthesized. Compounds were labeled with tritium for piroxicam-N(+) and carbon-14 for propoxicam-N(+). Pharmacokinetic studies conducted on rats showed that these molecules were able to highly concentrate in joint cartilages but their bioavailability by the oral way was low. Only propoxicam-N(+) exhibited a sufficient water solubility to be administered intravenously. This molecule was able to restore proteoglycans biosynthesis in cultured articular chondrocytes treated with Interleukin-1beta with an efficiency identical to that of indomethacin. These results suggest that the functionalization of oxicam derivatives by a quaternary ammonium group greatly increases their affinity toward articular cartilage without eliminating their pharmacological activity. New drugs synthesized according to this scheme could be useful to obtain a significant decrease of the efficient administered dose and consequently an attenuation of adverse effects such as digestive toxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5235-40
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
New quaternary ammonium oxicam derivatives targeted toward cartilage: synthesis, pharmacokinetic studies, and antiinflammatory potency.
pubmed:affiliation
INSERM Unité 484, Rue Montalembert, BP 184, 63005 Clermont-Ferrand Cedex, France.
pubmed:publicationType
Journal Article