Isoindoline compositions and methods for treating neurodegenerative disease
Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta-associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided.
1. A method of treating Alzheimer's disease comprising administering to a subject having said disease a total daily dose of 10 to 2000 mg, of a compound of the Formula:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 wherein the compound is
3. The method of claim 1 wherein the total daily dose is 10 to 300 mg.
4. The method of claim 1 wherein the total daily dose is 20 to 150 mg.
5. The method of claim 1 wherein the total daily dose is administered in a single dose.
6. The method of claim 1 wherein the total daily dose is administered in multiple doses per day.
7. The method of claim 1 wherein the compound is formulated in a capsule or tablet.
8. The method of claim 7 wherein the capsule or tablet comprises 10 to 200 mg of the compound or a pharmaceutically acceptable salt thereof.
9. The method of claim 7 wherein the wherein the total daily dose is 10 to 300 mg.
10. The method of claim 7 wherein the wherein the total daily dose is 20 to 150 mg.
11. The method of claim 1 wherein the compound is administered orally.
12. A method of treating Alzheimer's disease comprising administering to a subject having said disease a pharmaceutical composition comprising a compound of the Formula:
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient, wherein a total daily dose of the compound administered is 10 to 2000 mg.
13. The method of claim 12 wherein the compound is
14. The method of claim 12 wherein the total daily dose of the compound administered is 10 to 300 mg.
15. The method of claim 12 wherein the total daily dose of the compound administered is 20 to 150 mg.
16. The method of claim 12 wherein the total daily dose is administered in a single dose.
17. The method of claim 12 wherein the total daily dose is administered in multiple doses per day.
18. The method of claim 12 wherein the pharmaceutical composition is a capsule or tablet.
19. The method of claim 18 wherein the capsule or tablet comprises 10 to 200 mg of the compound or a pharmaceutically acceptable salt thereof.
20. The method of claim 18 wherein the wherein the total daily dose is 10 to 300 mg.
21. The method of claim 18 wherein the wherein the total daily dose is 20 to 150 mg.
22. The method of claim 12 wherein the pharmaceutical composition is administered orally.