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Use of S-Nitrosothiol Signaling to Treat Disordered Control of Breathing

a technology of s-nitrosothiol and signaling, which is applied in the direction of biocide, drug composition, peptide/protein ingredients, etc., can solve the problems of abnormal central control of ventilation, contribute to respiratory distress in newborn mammals and sleep apnea, and fail to breathe more often when oxygen levels are low, so as to increase the minute ventilation

Inactive Publication Date: 2009-01-01
GASTON BENJAMIN M +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Failure to breathe more often when oxygen levels are low can contribute to respiratory distress in newborn mammals and to sleep apnea in adults.
Abnormalities of central control of ventilation, particularly in response to hypoxia, can be life-threatening.
Furthermore, an apneic or hypoventilatory response to hypoxemia can occur in patients with obstructive sleep apnea, and abnormal dependence on hypoxic ventilatory drive can also make oxygen therapy life-threatening in patients with chronic obstructive lung diseases.
Current therapeutic options for each of these disorders are limited primarily to techniques involving artificial ventilation.
Of note, therapeutic options for respiratory alkalosis associated with acute hyperventilation (whether psychiatric or drug-induced) are similarly limited.

Method used

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  • Use of S-Nitrosothiol Signaling to Treat Disordered Control of Breathing

Examples

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example 1

SNOs Stimulate Respiratory Centers of the NTS to Increase VE

[0033]To test the hypothesis that SNOs stimulate respiratory centers of the NTS to increase VE, the ability of endogenous SNOs to increase VE in freely behaving, conscious rats using whole-body plethysmography was examined. CSNO, GSNO and CGSNO (1 nmol each) caused equivalent increases in VE, whereas D-CSNO had no effect (see FIG. 1; dose threshold for L-SNOs is 0.1 pmol). The exogenous NO donor, S-nitroso-N-acetyl-L-penicillamine, had similar but reduced effects (not shown). The L- and D-isomers of CSNO decayed at identical rates in rat brainstem homogenates (26% min—1 mg—1 protein each; P=not significant (NS)). Furthermore, neither excess 8-bromocyclic GMP nor glutathione had any effect on VE (n=3; P=NS).

[0034]Next, a low-mass fraction (less than a relative molecular mass of 10,000 (Mr 10K)) derived from deoxygenated blood was studied to determine whether the fraction would similarly increase VE. This fraction reproduced...

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Abstract

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-nitroso-L-cysteinyl glycine, N-acetyl cysteine and S-nitroso-N-acetyl cysteine. As shown in FIG. 1C the ability of endogenous SNOs to increase VE in freely behaving, conscious rats using whole-body plethysmography revealed that CSNO, GSNO and CGSNO (1 nmol each) caused 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).

Description

RELATED APPLICATION[0001]This application claims priority under 35 USC §199(e) to U.S. Provisional Application Ser. No. 60 / 313,548, filed Aug. 20, 2001, the disclosure of which is incorporated herein.US GOVERNMENT RIGHTS[0002]This invention was made with United States Government support under Grant Nos. HL 59337, awarded by the National Institutes of Health. The United States Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention is directed to compositions and methods for treating disordered control of breathing. More particularly, the present invention is directed to the use of S-nitrosothiols or other S-nitrosylating agents to enhance ventilation in patients suffering from a congenital or acquired brain stem abnormality.BACKGROUND OF THE INVENTION[0004]The ability to increase minute ventilation (VE=respiratory rate times tidal volume) in response to hypoxia is essential for survival. Failure to breathe more often when oxygen levels are lo...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/00A61K31/045A61K38/06A61P11/00A61K31/195A61K31/198A61K31/00A61K31/21
CPCA61K31/21A61K31/00A61P11/00A61P25/00
Inventor GASTON, BENJAMIN M.GOZAL, DAVID
Owner GASTON BENJAMIN M
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