Use of s-nitrosothiol signaling to treat disordered control...

A - Human Necessities – 61 – K

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A61K 38/06 (2006.01) A61K 9/72 (2006.01)

Patent

CA 2459647

The present invention is directed to a method of treating disordered control of breathing including the treatment of apnea and hypoventilation associated with congenital or acquired brain stem abnormalities. Specifically the invention is directed to treating disordered control of breathing by administering an S-nitrosylating agent selected from the group consisting of ethyl nitrite, glutathione, nitric oxide, S-nitrosocysteine, S- nitrosoglutathione, S-nitro-N-acetyl cysteine. As shown in Fig. 1C the ability of endogenous SNOs to increase VE in freely behaving, conscious rates using whole-body plethysmography revealed that CSNO, GSNO and CGSNO (1nmol each) caused equivalent increases in VE, whereas D-CSNO had no effect (left bar graph is the equivalent increases in VE, whereas D-CSNO had no effect (left bar graph is the control whereas the right bar represents administration of the respective SNO).

La présente invention concerne une méthode de traitement de troubles du contrôle respiratoire, notamment de l'apnée et de l'hypoventilation associées à des anomalies du tronc cérébral, congénitales ou acquises. En particulier, l'invention concerne le traitement de troubles du contrôle respiratoire par l'administration d'un agent de S-nitrosylation, sélectionné dans le groupe formé par le nitrite d'éthyle, le glutathion, le monoxyde d'azote, la S-nitrosocystéine, le S-nitrosoglutathion, la S-nitroso-L-cystéinyle glycine, la N-acétyle cystéine et la S-nitroso-N-acétyle cystéine. Comme le montre la figure (I), l'examen, par pléthysmographie corporelle, de la capacité de SNO endogènes à augmenter <I>V</I>¿E ?(ventilation par minute), chez des rats conscients et agissant librement, a révélé que CSNO, GSNO et CGSNO (1 nmol chaque) étaient à l'origine d'augmentations équivalentes de <I>V</I>¿E?, alors que D-CSNO n'avait aucun effet (la barre de gauche du diagramme représente le contrôle, et celle de droite représente l'administration de SNO respectives).

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