Treatments based on discovery that nitric oxide synthase is...

A - Human Necessities – 61 – K

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A61K 31/4425 (2006.01) A61K 31/00 (2006.01) A61K 31/198 (2006.01) A61K 31/223 (2006.01) A61K 31/44 (2006.01) A61K 31/444 (2006.01) A61K 31/4985 (2006.01) A61K 33/00 (2006.01)

Patent

CA 2386990

Paraquat has been found to accept electrons from nitric oxide synthase (NOS) whereupon the reduced paraquat generates toxic O2- and prevents NOS from giving electrons to arginine and thereby inhibits NO production. This is generalized for compounds with a redox potential greater than nitric oxide synthase. The compounds inhibit nitric oxide synthase and kill cells including NOS by generating O2- and also by depriving the cells of the NO which they need. Applications include treating paraquat-induced injury and pathologically proliferating cells (tumors, restenosis benign prostatic hypertrophy, pulmonary hypertension, infective pathogens).

Selon l'invention, le paraquat accepte des électrons de la synthase d'oxyde nitrique, le paraquat réduit produisant alors de l'O¿2??-¿ toxique et empêchant ladite synthase de donner des électrons à l'arginine, inhibant ainsi la production de l'oxyde nitrique. On généralise cela aux composés présentant un potentiel d'oxydo-réduction supérieur à la synthase d'oxyde nitrique. Les composés inhibent la synthase d'oxyde nitrique et éliminent des cellules renfermant ladite synthase en produisant de l'O¿2??-¿ et en privant les cellules de l'oxyde nitrique dont elles ont besoin. Les applications concernent notamment le traitement de blessures provoquées par le paraquat et de cellules pathologiquement proliférantes (tumeurs, resténose, hypertrophie prostatique bénigne, hypertension pulmonaire, agents infectieux).

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