H2 receptor antagonist compounds in combination with nitric oxide donors, compositions and methods of use

A composition comprising at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, and at least one compound that induces the production of endogenous nitric oxide or endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase.

A method for decreasing or reversing gastrointestinal toxicity or facilitating ulcer healing resulting from administration of a nonsteroidal antiinflammatory drug to a patient comprising administering to a patient in need thereof a therapeutically effective amount of at least one nonsteroidal antiinflammatory drug, at least one H2 receptor antagonist compound, and at least compound selected from an S-nitrosothiol, L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, citrulline, ornithine, glutamine, a compound that comprises at least one ON—C-group, a compound that comprises at least one ON—C— group, and an N-oxo-N-nitrosoamine having the formula:

• R1R2N—N(O—M+)—NO, wherein R1 and R2 are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+ is an organic or inorganic cation.

A method for preventing or treating a gastrointestinal disorder, facilitating ulcer healing, or decreasing the recurrence of an ulcer in a patient in need thereof comprising administering to the patient a therapeutically effective amount of at least one H2 receptor antagonist or a pharmaceutically acceptable salt thereof, and at least one compound selected from an S-nitrosothiol, L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, citrulline, ornithine, glutamine, a compound that comprises at least one ON—O-group, a compound that comprises at least one ON—C— group, and an N-oxo-N-nitrosoamine having the formula:

• R1R2N—N(O—M+)—NO, wherein R1 and R2 are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+is an organic or inorganic cation.

A kit comprising at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, and at least one compound selected from an S-nitrosothiol, L-arginine, L-homoarginine, N-hydroxy-L-arginine, nitrosated L-arginine, nitrosylated L-arginine, nitrosated N-hydroxy-L-arginine, nitrosylated N-hydroxy-L-arginine, citrulline, ornithine, glutamine, a compound that comprises at least one ON—O-group, a compound that comprises at least one ON—C— group, and an N-oxo-N-nitrosoamine having the formula:

• R1R2N—N(O—M+)—NO, wherein R1 and R2 are each independently a polypeptide, an amino acid, a sugar, an oligonucleotide, a straight or branched, saturated or unsaturated, aliphatic or aromatic, substituted or unsubstituted hydrocarbon, or a heterocyclic group, and M+ is an organic or inorganic cation.

A composition comprising at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, in combination with at least one compound that comprises at least one O2N—O—, O2N—N—, O2N—S— or —O2N—C— group.

A kit comprising at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, and at least one compound that comprises at least one O2N—O—, O2N—N—, O2N—S— or —O2N—C— group.

A method for preventing or treating a gastrointestinal disorder, facilitating ulcer healing, or decreasing the recurrence of an ulcer in a patient in need thereof comprising administering to a patient in need thereof a therapeutically effective amount of at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, in combination with at least one compound that comprises at least one O2N—O—, O2N—N—, O2N—S— or —O2N—C— group.

A method for decreasing or reversing gastrointestinal toxicity or facilitating ulcer healing resulting from administration of a nonsteroidal antiinflammatory drug to a patient comprising administering to a patient in need thereof a therapeutically effective amount of at least one H2 receptor antagonist compound or a pharmaceutically acceptable salt thereof, in combination with at least one compound that comprises at least one O2N—O—, O2N—N—, O2N—S— or —O2N—C— group.