Method of using tetracycline compounds for inhibition of...

A - Human Necessities – 61 – K

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A61K 31/65 (2006.01) A61P 19/02 (2006.01)

Patent

CA 2264552

The invention is a method of inhibiting the production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo biological system. The method employs a tetracycline compound to inhibit the production of NO and/or to inhibit the expression or activity of an inducible isoform ot nitric oxide synthase (iNOS). Preferably, the tetraclycine compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the biological system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetraclycine compounds are tetracycline compounds which have been modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.

L'invention concerne un procédé d'inhibition de la production de monoxyde d'azote (NO) dans un système biologique in vivo, in vitro ou ex vivo. Dans ce procédé on emploie un composé tétracycline afin d'inhiber la production de NO et/ou l'expression ou l'activité d'un isoforme inductible de la NO synthétase (iNOS). De préférence, ce composé tétracycline possède une activité inhibitrice à l'égard des métalloprotéinases. De même, on préfère que ce composé tétracycline soit apporté au système biologique en dose présentant peu ou pas d'activité antibactérienne dans le système. En conséquence, des composés tétracycline préférés sont ceux modifiés aux fins de réduction ou d'élimination de leur activité antimicrobienne. On peut utiliser ce procédé pour traiter des états pathologiques chez des mammifères, états caractérisés par une production de NO induite par iNOS, notamment, par exemple, les états inflammatoires.

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