Methods of reducing angiogenesis
View Patent ↗The present invention provides methods of reducing angiogenesis in an individual. The methods generally involve administering to the individual an effective amount of a nicotinic acetyl choline receptor antagonist. The methods are useful to treat conditions associated with or resulting from angiogenesis, particularly pathological angiogenesis. The invention further provides methods of treating a condition associated with or resulting from angiogenesis.
1. A method of treating a disorder associated with pathological angiogenesis in a mammal, the method comprising administering to a mammal having a disorder associated with pathological angiogenesis mecamylamine or a pharmaceutically acceptable salt thereof in an amount effective to reduce pathological angiogenesis.
2. The method of claim 1 , wherein the disorder is an ocular disease.
3. The method of claim 2 , wherein said ocular disease is selected from diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, retrolental fibroplasia, neovascular glaucoma, rubeosis, and macular degeneration.
4. The method of claim 3 , wherein the ocular disease is corneal graft rejection.
5. The method of claim 3 , wherein said ocular disease is macular degeneration.
6. The method of claim 3 , wherein said ocular disease is neovascular glaucoma.
7. The method of claim 3 , wherein said ocular disease is retinopathy of prematurity.
8. The method of claim 2 , wherein the ocular disease is a proliferative retinopathy.
9. The method of claim 2 , wherein the ocular disease is age-related maculopathy, retrolental fibroplasia, or diabetic retinopathy.
10. The method of claim 1 , wherein the disorder is rheumatoid arthritis.
11. The method of claim 1 , wherein the disorder is psoriasis.
12. The method of claim 1 , wherein the disorder is a cancer.
13. The method of claim 12 , wherein the cancer is a colon carcinoma.
14. The method of claim 12 , wherein the cancer is a lung carcinoma.
15. The method of claim 12 , wherein the cancer is a carcinoma of the rectum.
16. The method of claim 12 , wherein the cancer is a kidney carcinoma.
17. The method of claim 12 , wherein the cancer is a breast carcinoma.
18. The method of claim 12 , further comprising administering at least one additional cancer chemotherapeutic agent.
19. The method of claim 18 , wherein the at least one additional cancer chemotherapeutic agent is an alkylating agent.
20. The method of claim 18 , wherein the at least one additional cancer chemotherapeutic agent is 5-fluorouracil.
21. The method of claim 1 , wherein the disorder is atherosclerosis.
22. The method of claim 1 , wherein the mammal is a human.
23. The method of claim 1 , further comprising administering at least one additional anti-angiogenic agent.
24. The method of claim 23 , where the anti-angiogenic agent is a neutralizing monoclonal antibody directed against a growth factor.
25. The method of claim 2 , further comprising administering at least one additional anti-angiogenic agent.
26. The method of claim 25 , where the anti-angiogenic agent is a neutralizing monoclonal antibody directed against a growth factor.
27. The method of claim 1 , wherein the mecamylamine is a free base.
28. The method of claim 1 , wherein the mecamylamine is administered as a pharmaceutically acceptable salt.
29. A method of treating an ocular disease associated with pathological angiogenesis, the method comprising administering to a mammal having an ocular disease associated with pathological angiogenesis a nicotinic acetylcholine receptor (nAChR) antagonist or a pharmaceutically acceptable salt thereof in an amount effective to treat the ocular disease, wherein the nAChR antagonist is not tetraethylammonium.
30. The method of claim 29 , wherein said ocular disease is selected from diabetic retinopathy, retinopathy of prematurity, corneal graft rejection, retrolental fibroplasia, neovascular glaucoma, rubeosis, and macular degeneration.
31. The method of claim 29 , wherein the ocular disease is retinopathy of prematurity.
32. The method of claim 29 , wherein said ocular disease is macular degeneration.
33. The method of claim 29 , wherein the ocular disease is diabetic retinopathy.
34. The method of claim 29 , wherein the nAChR antagonist is selected from the group consisting of mecamylamine; hexamethonium, dihydro-beta-erythroidine, d-tubocurarine, pempidine, chlorisondamine, erysodine, trimethaphan camsylate, pentolinium, bungarotoxin, succinylcholine, trimethaphan, chlorisondamine, and trimethidinium.
35. The method of claim 29 , wherein the nAChR antagonist is a free base.
36. The method of claim 29 , wherein the nAChR antagonist is administered as a pharmaceutically acceptable salt.
37. The method of claim 29 , wherein the nAChR antagonist is hexamethonium.
38. The method of claim 29 , wherein the mammal is a human.
39. The method of claim 29 , further comprising administering at least one additional anti-angiogenic agent.
40. The method of claim 39 , where the anti-angiogenic agent is a neutralizing monoclonal antibody directed against a growth factor.
41. A method of treating psoriasis in a mammal having psoriasis, the method comprising administering to the mammal having psoriasis a nicotinic acetylcholine receptor (nAChR) antagonist or a pharmaceutically acceptable salt thereof in an amount effective to treat the psoriasis.
42. The method of claim 41 , wherein the nAChR antagonist is selected from mecamylamine; hexamethonium, dihydro-beta-erythroidine, d-tubocurarine, pempidine, chlorisondamine, erysodine, trimethaphan camsylate, pentolinium, bungarotoxin, succinylcholine, tetraethylammonium, trimethaphan, chlorisondamine, and trimethidinium.
43. The method of claim 41 , wherein the nAChR antagonist is hexamethonium.
44. The method of claim 41 , further comprising administering at least one additional anti-angiogenic agent.
45. The method of claim 41 , wherein the mammal is a human.
46. The method of claim 41 , wherein the nAChR antagonist is a free base.
47. The method of claim 41 , wherein the nAChR antagonist is administered as a pharmaceutically acceptable salt.
48. The method of claim 41 , further comprising administering at least one additional anti-angiogenic agent.
49. The method of claim 48 , where the anti-angiogenic agent is a neutralizing monoclonal antibody directed against a growth factor.