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1. (WO2001032167) ENDOGENOUS NITRIC OXIDE SYNTHESIS UNDER CONDITIONS OF LOW OXYGEN TENSION

Pub. No.:    WO/2001/032167    International Application No.:    PCT/US2000/029371
Publication Date: Fri May 11 01:59:59 CEST 2001 International Filing Date: Fri Oct 27 01:59:59 CEST 2000
IPC: A61K 31/195
A61K 45/06
Applicants: NITROMED, INC.
SAENZ DE TEJADA, Inigo
Inventors: SAENZ DE TEJADA, Inigo
Title: ENDOGENOUS NITRIC OXIDE SYNTHESIS UNDER CONDITIONS OF LOW OXYGEN TENSION
Abstract:
The present invention provides methods of promoting synthesis of nitric oxide or endothelium-derived relaxing factor (EDRF) in hypoxic mammalian tissues by administering at least one N-hydroxyguanidine compound that is a substrate of nitric oxide synthase and at least one thromboxane inhibitor, and, optionally, one or more vasoactive agents. The present invention also provides methods of promoting vasorelaxation and treating sexual dysfunctions in patients by administering at least one N-hydroxyguanidine compounds that is a substrate for nitric oxide synthase and at least one thromboxane inhibitor, and, optionally, one or more vasoactive agents. The present invention also provides methods for treating clinical conditions resulting from hypoxic conditions such as pulmonary disease, cardiovascular disorders, circulatory hypoxia, specific organ hypoxia, localized hypoxia, edema, central nervous system disorders, memory loss, or arterial disease. The present invention also provides methods for treating clinical conditions resulting from a high level of arginase activity, such as, heart disease, systemic hypertension, pulmonary hypertension, sexual dysfunction, autoimmune disease, chronic renal failure and cerebral vasospasm. The present invention also provides methods for treating clinical conditions associated with a deficient nitric oxide pathway by the administration of at least one N-hydroxyguanidine compound and at least one thromboxane inhibitor, and, optionally, one or more vasoactive agents. The present invention also provides pharmaceutical compositions comprising at least one N-hydroxyguanidine compound and at least one thromboxane inhibitor, and, optionally, one or more vasoactive agents.