DRY EYE TREATMENTS
Described herein are methods and pharmaceutical formulations for treating dry eye disease.
1 . A method of treating dry eye, comprising the local administration of a therapeutically effective amount of a nicotinic acetylcholine receptor agonist into the nasal cavity of an individual in need thereof, wherein the agonist selectively binds to the peripheral nicotinic acetylcholine receptor.
2 . The method of claim 1 , wherein the agonist does not cross the blood-brain barrier in a pharmacologically relevant concentration.
3 . The method of claim 1 , wherein the agonist selectively binds to at least one of the peripheral nicotinic acetylcholine receptor subtypes selected from alpha3beta4, alpha4beta2, and alpha7.
4 . The method of claim 1 , wherein the agonist is administered in an amount that is not systemically bioavailable.
5 . The method of claim 1 , wherein the agonist selectively binds to the peripheral nicotinic acetylcholine receptor in an amount that does not result in undesired psychoactive side effects.
6 . The method of claim 1 , wherein the agonist selectively binds to the peripheral nicotinic acetylcholine receptor in an amount that does not result in undesired systemic side effects.
7 . 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 the nicotinic acetylcholine receptor from the desensitized state.
8 . The method of claim 7 , wherein the one or more substances are selected from 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.
9 . The method of claim 8 , wherein the calcineurin inhibitor is selected from cyclosporine, pimecrolimus, and tacrolimus.
10 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is selected from cytisine, epibatidine, varenicline, tebanicline, DBO-83, CC4, ABT-418, ABT-366833, ABT-202, ABT-894, SIB-1663, GTS-21, PHA-543613, PNU-282987, LY-2087101, A85380, and 5-I-A85380.
11 . The method of claim 1 , wherein at least 5 micrograms of the nicotinic acetylcholine receptor agonist is administered into the nasal cavity.
12 . The method of claim 1 , wherein at least 100 micrograms of the nicotinic acetylcholine receptor agonist is administered into the nasal cavity.
13 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is administered at least once daily.
14 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is administered at least twice daily.
15 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is administered at least once weekly.
16 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is administered into the nasal cavity as a liquid, suspension, aerosol, gel, ointment, dry powder, cream, paste, lotion, or balm.
17 . The method of claim 1 , wherein the nicotinic acetylcholine receptor agonist is administered into the nasal cavity by a syringe, dropper, bottle nebulizer, atomization pump, inhaler, powder spray device, vaporizer, patch, medicated stick, pipette, or jet of liquid.
18 . The method of claim 1 , wherein the trigeminal nerve is activated.
19 . The method of claim 18 , wherein the anterior ethmoidal nerve is activated.
20 . The method of claim 1 , wherein the nasolacrimal reflex is activated.