Methods for remodeling neuronal and cardiovascular pathways

Abstract

The present invention provides a method of administration of an agent which acts to remodel neuronal or vascular pathways for the long term management of sexual dysfunction in both males and females. In a preferred embodiment, the invention provides a method of ameliorating or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia comprising administering to a human patient in need of such treatment a therapeutically effective amount of an anti-pressor agent. The anti-pressor agent comprises one or more compounds selected from the therapeutic classes of direct vasodilators such as hydralazine and NO donors, ACE inhibitors, angiotensin-II receptor antagonists, α 1 -adrenergic receptor antagonists, β-adrenergic receptor antagonists, calcium channel blockers, and phosphodiesterase inhibitors. The anti-pressor agent may be co-administered with a diuretic compound, and is administered either chronically at low dose, or for short periods of time at doses higher than are typically used for the treatment of hypertension. In certain embodiments of the method of the invention, the anti-pressor agent is co-administered with a diuretic agent and/or prostaglandin-E 1 .

1 - 33 : Canceled  
     
     
         34 . A method for treating a sexual dysfunction, comprising administering to a human patient in need thereof a therapeutically effective amount of an anti-pressor agent over a short period of time at a dose higher than that used to treat hypertension, wherein said anti-pressor agent comprises a renin angiotensin system inhibitor.  
     
     
         35 . The method of  claim 34 , wherein said anti-pressor agent is a renin angiotensin system inhibitor selected from the group consisting of ACE inhibitors and angiotensin-II receptor antagonists.  
     
     
         36 . The method of  claim 35 , wherein said ACE inhibitor is selected from the group consisting of alacepril, benazepril, captopril, ceronapril, cilazapril, delapril, enalapril, fosinopril, imidapril, lacidipine, libenzapril, lisinopril, moexipril, moveltipril, pentopril, perindopril, quinapril, ramipril, spirapril, temocapril, and trandolapril.  
     
     
         37 . The method of  claim 35 , wherein said angiotensin-II receptor antagonist is selected from the group consisting of eprosartan, irbesartan, losartan, and valsartan.  
     
     
         38 . The method of  claim 35 , wherein said anti-pressor agent further comprises one or more compounds selected from the group consisting of prostaglandin-E 1 , α 1 -adrenergic receptor antagonists, β-adrenergic receptor antagonists, calcium channel blockers, direct acting vasodilators, NO donors, activators of guanylyl cyclase, activators of adenyl cyclase, and phosphodiesterase inhibitors.  
     
     
         39 . The method of  claim 38 , wherein said α 1 -adrenergic receptor antagonist is selected from the group consisting of alfuzosin, apraclonidine, bunazosin, carvedilol, clonidine, dapiprazole, doxazosin, indoramin, labetolol, midrodrine, naphazoline, phenoxybenzamine, phentolamine, prazosin, tamsulosin, terazosin, trimazosin, and urapidil.  
     
     
         40 . The method of  claim 38 , wherein said calcium channel blocker is selected from the group consisting of bepridil, diltiazem, mibrefadil, nicardipine, nifedipine, nimopidine, and verapamil.  
     
     
         41 . The method of  claim 38 , wherein said direct acting vasodilator is selected from the group consisting of hydralazine and NO donors.  
     
     
         42 . The method of  claim 41 , wherein said NO donor is selected from the group consisting of glyceryl trinitrate, isosorbide 5-mononitrate, isosorbide dinitrate, pentaerythritol tetranitrate, sodium nitroprusside, 3-morpholinosydnonimine, molsidnomine, S-nitroso-N-acetylpenicillamine, S-nitrosoglutathione, N-hydroxyl-L-arginine, S,S-dinitrosodthiol, and NO gas.  
     
     
         43 . The method of  claim 38 , wherein said activator of guanylyl cyclase or adenyl cyclase is selected from the group consisting of YC-1 and forskolin.  
     
     
         44 . The method of  claim 38 , wherein said phosphodiesterase inhibitor is amrinone.  
     
     
         45 . The method of  claim 38 , wherein said phosphodiesterase inhibitor is sildenafil.  
     
     
         46 . The method of  claim 34 , wherein said anti-pressor agent is administered for a period of time ranging between about five days to about twenty-one days.  
     
     
         47 . The method of  claim 34 , wherein said anti-pressor agent is administered for a period of time ranging between about five days to about twenty-one days and repeated following a period of no treatment with said anti-pressor agent.  
     
     
         48 . The method of  claim 34 , wherein said anti-pressor agent is administered at a dose ranging between about 1.5 to about 3 times the dose used for the treatment of hypertension.  
     
     
         49 . The method of  claim 34 , wherein said anti-pressor agent is administered for the amelioration, inhibition, or reversal of pathogenic vascular degradative modeling associated with a sexual dysfunction.  
     
     
         50 . The method of  claim 34 , wherein said anti-pressor agent is administered to a normotensive patient.  
     
     
         51 . The method of  claim 46 , wherein said anti-pressor agent is administered to a normotensive patient.  
     
     
         52 . The method of  claim 47 , wherein said anti-pressor agent is administered to a normotensive patient.  
     
     
         53 . The method of  claim 34 , wherein said human patient is male.  
     
     
         54 . The method of  claim 34 , wherein said human patient is female.  
     
     
         55 . The method of  claim 34 , wherein the treating of sexual dysfunction is by ameliorating, inhibiting or reversing pathogenic vascular degradative modeling in the ilio-hypogastric-pudendal arterial bed and genitalia.