Methods of treating ocular conditions

1. A method of treating dry eye, comprising the local administration of a therapeutically effective amount of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of an individual in need thereof.

2. The method of claim 1 , wherein the pharmaceutically acceptable salt is a galactarate or citrate salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine.

3. The method of claim 1 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate.

4. The method of claim 1 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate.

5. The method of claim 1 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate dihydrate or (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate monohydrate.

6. The method of claim 1 , comprising administering between 1 microgram and 5 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

7. The method of claim 1 , comprising administering between 1 microgram and 2 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

8. The method of claim 1 , comprising administering between 100 micrograms and 1000 micrograms of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

9. The method of claim 1 , further comprising the local administration of one or more substances that prevent the entry or reduce the entry of the nicotinic acetylcholine receptor into the desensitized state, or facilitate the recovery of a peripheral nicotinic acetylcholine receptor from the desensitized state.

10. The method of claim 9 , wherein the one or more substances are selected from the group consisting of protein kinase C (PKC) or factors that upregulate or up-modulate PKC, cAMP-dependent protein kinase (PKA) or factors that upregulate or up-modulate PKA, and calcineurin inhibitors.

11. The method of claim 10 , wherein the calcineurin inhibitor is selected from the group consisting of cyclosporine, pimecrolimus, and tacrolimus.

12. The method of claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least once daily.

13. The method of claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least twice daily.

14. The method of claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered as a liquid, suspension, aerosol, gel, ointment, dry powder, cream, paste, lotion, or balm.

15. The method of claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered by a syringe, dropper, bottle nebulizer, atomization pump, inhaler, powder spray device, vaporizer, patch, medicated stick, pipette, or jet of liquid.

16. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 10 mg/mL and 25 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

17. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 5 mg/mL and 50 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 5 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

19. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 10 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

20. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after LASIK eye surgery.

21. A method of treating ocular discomfort, comprising the local administration of a therapeutically effective amount of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of an individual in need thereof.

22. The method of claim 21 , wherein the pharmaceutically acceptable salt is a galactarate or citrate salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine.

23. The method of claim 21 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate.

24. The method of claim 21 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate.

25. The method of claim 21 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate dihydrate or (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate monohydrate.

26. The method of claim 21 , comprising administering between 1 microgram and 5 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

27. The method of claim 21 , comprising administering between 1 microgram and 2 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

28. The method of claim 21 , comprising administering between 100 micrograms and 1000 micrograms of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

29. The method of claim 21 , further comprising the local administration of one or more substances that prevent the entry or reduce the entry of the nicotinic acetylcholine receptor into the desensitized state, or facilitate the recovery of a peripheral nicotinic acetylcholine receptor from the desensitized state.

30. The method of claim 29 , wherein the one or more substances are selected from the group consisting of protein kinase C (PKC) or factors that upregulate or up-modulate PKC, cAMP-dependent protein kinase (PKA) or factors that upregulate or up-modulate PKA, and calcineurin inhibitors.

31. The method of claim 30 , wherein the calcineurin inhibitor is selected from the group consisting of cyclosporine, pimecrolimus, and tacrolimus.

32. The method of claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least once daily.

33. The method of claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least twice daily.

34. The method of claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered as a liquid, suspension, aerosol, gel, ointment, dry powder, cream, paste, lotion, or balm.

35. The method of claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered by a syringe, dropper, bottle nebulizer, atomization pump, inhaler, powder spray device, vaporizer, patch, medicated stick, pipette, or jet of liquid.

36. The method of claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 10 mg/mL and 25 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

37. The method of claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 5 mg/mL and 50 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

38. The method of claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 5 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

39. The method of claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 10 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

40. The method of claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after LASIK eye surgery.

41. A method of increasing tear production, comprising the local administration of a therapeutically effective amount of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of an individual in need thereof.

42. The method of claim 41 , wherein the pharmaceutically acceptable salt is a galactarate or citrate salt of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine.

43. The method of claim 41 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate.

44. The method of claim 41 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate.

45. The method of claim 41 , wherein the pharmaceutically acceptable salt is (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate dihydrate or (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine hemigalactarate monohydrate.

46. The method of claim 41 , comprising administering between 1 microgram and 5 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

47. The method of claim 41 , comprising administering between 1 microgram and 2 milligrams of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

48. The method of claim 41 , comprising administering between 100 micrograms and 1000 micrograms of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, in alternating nostrils of the individual in need thereof.

49. The method of claim 41 , further comprising the local administration of one or more substances that prevent the entry or reduce the entry of the nicotinic acetylcholine receptor into the desensitized state, or facilitate the recovery of a peripheral nicotinic acetylcholine receptor from the desensitized state.

50. The method of claim 49 , wherein the one or more substances are selected from the group consisting of protein kinase C (PKC) or factors that upregulate or up-modulate PKC, cAMP-dependent protein kinase (PKA) or factors that upregulate or up-modulate PKA, and calcineurin inhibitors.

51. The method of claim 50 , wherein the calcineurin inhibitor is selected from the group consisting of cyclosporine, pimecrolimus, and tacrolimus.

52. The method of claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least once daily.

53. The method of claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered at least twice daily.

54. The method of claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered as a liquid, suspension, aerosol, gel, ointment, dry powder, cream, paste, lotion, or balm.

55. The method of claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered by a syringe, dropper, bottle nebulizer, atomization pump, inhaler, powder spray device, vaporizer, patch, medicated stick, pipette, or jet of liquid.

56. The method of claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 10 mg/mL and 25 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

57. The method of claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising between 5 mg/mL and 50 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

58. The method of claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 5 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

59. The method of claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 10 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

60. The method of claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after LASIK eye surgery.

61. The method according to claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered with a medical device.

62. The method according to claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered with a medical device.

63. The method according to claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered with a medical device.

64. The method according to claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 1 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

65. The method according to claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 1 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

66. The method according to claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 1 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

67. The method according to claim 1 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 6 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

68. The method according to claim 21 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 6 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

69. The method according to claim 41 , wherein (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered in a pharmaceutical formulation for nasal administration comprising about 6 mg/mL of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof.

70. The method according to claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after an ophthalmologic surgical procedure.

71. The method according to claim 21 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after an ophthalmologic surgical procedure.

72. The method according to claim 41 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, or a pharmaceutically acceptable salt thereof, is administered prior to or after an ophthalmologic surgical procedure.