Non-retinoid antagonists for treatment of age-related macular degeneration and stargardt disease
A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in mammals afflicted therewith, comprising administering to the mammal an effective amount of a non-retinoid antagonist compound or a pharmaceutically acceptable salt thereof.
1. A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in mammal afflicted therewith, comprising administering to the mammal an effective amount of a compound having the structure:
wherein
n=2 or 3;
R 1 is absent or present and when present, is CH 3 or O;
α is absent or present,
wherein when α present, then R 1 is O, and when α is absent, then R 1 is CH 3 ;
X is
Y is N or C;
Z is
and
when n=2, R 1 is absent, X is
and Y is C,
then Z is other than
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the compound has the structure
or a pharmaceutically acceptable salt thereof.
3. The method of claim 1 wherein the disease is further characterized by bisretinoid-mediated macular degeneration.
4. The method of claim 3 , wherein the amount of the compound is effective to lower the serum concentration of RBP4 in the mammal.
5. The method of claim 3 , wherein the amount of the compound is effective to lower the retinal concentration of a bisretinoid in lipofuscin in the mammal.
6. The method of claim 3 , wherein the bisretinoid is A2E.
7. The method of claim 3 , wherein the bisretinoid is isoA2E.
8. The method of claim 3 , wherein the bisretinoid is A2-DHP-PE.
9. The method of claim 3 , wherein the bisretinoid is atRAL di-PE.
10. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Age-Related Macular Degeneration.
11. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is dry (atrophic) Age-Related Macular Degeneration.
12. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Stargardt Disease.
13. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Best disease.
14. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is adult vitelliform maculopathy.
15. The method of claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Stargardt-like macular dystrophy.