US2009297497A1PendingUtilityA1

Methods and compositions for treating nephrogenic diabetes and insipidus

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Individually held — no corporate assignee on recordPriority: Oct 25, 2004Filed: Oct 21, 2005Published: Dec 3, 2009
Est. expiryOct 25, 2024(expired)· nominal 20-yr term from priority
Inventors:Bellamkonda K. KishoreNoel G. CarlsonDonald E. KohanRaoul D. Nelson
A61P 5/10A61K 45/06A61K 31/675A61K 31/7072A61K 31/18A61K 31/00A61K 31/365A61K 31/4965A61K 31/7076A61P 13/00A61K 38/46C12Y 306/01005A61K 31/405A61K 31/53A61K 31/5575A61K 31/549A61K 31/185A61K 31/192
37
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Claims

Abstract

Disclosed are compositions and methods for treating nephrogenic diabetes insipidus and for induction of diuretic effect.

Claims

exact text as granted — not AI-modified
1 . A method of treating nephrogenic diabetes insipidus (NDI) in a subject, comprising administering a composition to the subject, wherein the composition is an antagonist of a P2Y purinergic receptor. 
     
     
         2 . The method of  claim 1 , wherein the P2Y purinergic receptor is a P2Y2 purinergic receptor. 
     
     
         3 . The method of  claim 1 , wherein the antagonist is P2Y selective antagonist. 
     
     
         4 . The method of  claim 1 , wherein the antagonist decreases the level of PGE2 in the kidney. 
     
     
         5 . The method of  claim 1 , wherein the antagonist decreases the interaction of the P2Y receptor and PGE2. 
     
     
         6 . A method of modulating NDI in a subject, comprising administering a composition to the subject, wherein the composition is an antagonist of a P2Y purinergic receptor. 
     
     
         7 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with inhibitors of prostaglandin synthesis. 
     
     
         8 . The method of  claim 7 , wherein the inhibitor is a non-specific one for cyclooxygenases. 
     
     
         9 . The method of  claim 8 , wherein the inhibitor is indomethacin, rofecoxib, or flurbiprofen. 
     
     
         10 . The method of  claim 8 , wherein the inhibitor inhibits cyclooxygenase-1. 
     
     
         11 . The method of  claim 8 , wherein the inhibitor inhibits cyclooxygenase-2. 
     
     
         12 . The method of  claim 7 , wherein more than one inhibitor of prostaglandin synthesis is used with the P2Y antagonist. 
     
     
         13 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with inhibitors of arachidonic acid release. 
     
     
         14 . The method of  claim 1 , wherein the P2Y antagonist is used in combination 
     
     
         14 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a composition that increases cAMP. 
     
     
         15 . The method of  claim 14 , wherein the composition that increases cAMP is an inhibitor of phosphodiesterases (PDES). 
     
     
         16 . The method of  claim 14  wherein the composition that increases cAMP is an enhancer of adenylyl cyclase (AC). 
     
     
         17 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a PKA activator. 
     
     
         18 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a composition that inhibits protein kinase C(PKC). 
     
     
         19 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a composition that inhibits MAP kinase kinase. 
     
     
         20 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a diuretic. 
     
     
         21 . The method of  claim 20 , wherein the diuretic is a thiazide. 
     
     
         22 . The method of  claim 20 , wherein a potassium sparing diuretic is also used. 
     
     
         23 . The method of  claim 22 , wherein the potassium sparing diuretic is amiloride. 
     
     
         24 . The method of  claim 1 , wherein thiazide is used in combination with a prostaglandin synthesis inhibitor. 
     
     
         25 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a non-specific blocker of prostanoid receptors. 
     
     
         26 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a selective blocker of prostanoid receptors. 
     
     
         27 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with a non-specific or specific blockers of prostaglandin transporters (PGT). 
     
     
         28 . The method of  claim 1 , wherein the P2Y antagonist is used in combination with an agent that inhibits or blocks the release of prostaglandins from cells. 
     
     
         29 . The method of  claim 1 , wherein the P2Y receptor antagonist is used in combination with agents that enhance the degradation or inactivation of prostaglandins released from the cells. 
     
     
         30 . A method of treating fluid retention comprising administering to a subject in need thereof an effective amount of a P2Y agonist. 
     
     
         31 . A method of treating polyuria or hypematremia comprising administering to a subject in need thereof an effective amount of apyrase or any nucleotide hydrolyzing enzymes, such as NTPDases. 
     
     
         32 . The method of  claim 1 , wherein an effective amount of apyrase is administered in combination with an antagonist of a P2Y purinergic receptor. 
     
     
         33 . A method of treatment where a P2Y2 receptor agonist is used alone or in combination with another agent for the purpose of achieving diuretic effect.

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