Nitrosated and nitrosylated prostaglandins, compositions and methods of use
View Patent ↗The invention describes novel nitrosated and/or nitrosylated prostaglandins, and novel compositions comprising at least one nitrosated and/or nitrosylated prostaglandin, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase, and/or at least one vasoactive agent. The invention also provides novel compositions comprising at least one prostaglandin and at least one S-nitrosothiol compound, and, optionally, at least one vasoactive agent. The prostaglandin is preferably a prostaglandin E 1 compound, more preferably alprostadil, and the S-nitrosothiol compound is preferably S-nitrosoglutathione. The invention also provides methods for treating or preventing sexual dysfunctions in males and females, for enhancing sexual responses in males and females, and for treating or preventing cerebrovascular disorders, cardiovascular disorders, benign prostatic hyperplasia (BPH), glaucoma, peptic ulcers or for inducing abortions.
1. A method for treating erectile dysfunction in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a composition comprising a compound selected from the group consisting of:
(2S,3S)-2,3,4-tris(nitroxy)butyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R, 4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate;
(2S)-2,3-bis(nitroxy)propyl 7-[5-((1E)(3S)-3-(nitrooxyoct-1-enyl)(1R,4R,5R)-4-(nitrooxy)-2-oxocyclopentyl]heptanoate;
3-nitrooxy-2,2-bis(nitrooxymethyl)propyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate;
3-nitrooxy-2,2-bis[(nitrooxy)methyl]propyl 7-[5-[(1E)(3S)-3-(nitrooxyoct-1-enyl)(1R,4R,5R)-4-nitrooxy-2-oxocyclopentyl]heptanoate;
methyl 7-[5-((1E)(3S)-3-nitroxyoct-1-enyl)(1R,4R,5R)-4-nitrooxy-2-oxocyclopentyl]heptanoate;
2-[2-(nitrosothio)adamantan-2-yl]ethyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate;
[{1-[(4-methylphenyl)sulfonyl]-4-(nitrosothiol)-4-piperidyl}methyl 7-[5-((1E) (3S)-3-hydroxyoct-1-enyl)(1R,4R,5R)-4-hydroxy-2-oxocyclopentyl]heptanoate; and
2-methyl-2-(nitrosothio)propyl 7-[5-((1E)(3S)-3-hydroxyoct-1-enyl)(1R,4R, 5R)-4-hydroxy-2-oxocyclopentyl]heptanoate;
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the composition further comprises (i) at least one vasoactive agent; (ii) at least one nitric oxide donor compound; or (iii) at least one vasoactive agent and at least one nitric oxide donor compound.
3. The method of claim 2 , wherein the vasoactive agent is a potassium channel activator, a calcium channel blocker, an α-blocker, a β-blocker, a phosphodiesterase inhibitor, adenosine, an ergot alkaloid, a vasoactive intestinal peptide, a dopamine agonist, an opioid antagonist, an endothelin antagonist or a mixture thereof.
4. The method of claim 3 wherein the vasoactive agent is an α-blocker or a phosphodiesterase inhibitor.
5. The method of claim 4 , wherein the α-blocker is phentolamine, prazosin, doxazosin, terazosin, yohimbine or moxisylyte and the phosphodiesterase inhibitor is papaverine, zaprinast, sildenafil or IC 351, or a mixture thereof.
6. The method of claim 1 , wherein the composition is administered orally, by intracavernosal injection, by transurethral application, or by transdermal application.