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 dose of about 0.01 mg/kg/day to about 25 mg/kg/day, of a compound of the Formula:
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 wherein the compound pharmaceutically acceptable salt is
3. The method of claim 1 wherein the dose is about 0.1 mg/kg/day to about 10 mg/kg/day.
4. The method of claim 1 wherein the dose is about 0.2 mg/kg/day to about 5 mg/kg/day.
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 or pharmaceutically acceptable salt thereof is formulated in a capsule or tablet.
8. The method of claim 7 wherein the capsule or tablet comprises 0.1 mg/kg/day to about 10 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.
9. The method of claim 7 wherein the capsule or tablet comprises 0.2 mg/kg/day to about 5 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.
10. The method of claim 1 wherein the compound or pharmaceutically acceptable salt thereof is administered orally.
11. 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 dose of the compound or pharmaceutically acceptable salt thereof is administered is 0.01 mg/kg/day to about 25 mg/kg/day.
12. The method of claim 11 wherein the pharmaceutically acceptable salt is
13. The method of claim 11 wherein the total daily dose of the compound administered is about 0.1 mg/kg/day to about 10 mg/kg/day.
14. The method of claim 11 wherein the total daily dose of the compound administered is about 0.2 mg/kg/day to about 5 mg/kg/day.
15. The method of claim 11 wherein the dose is administered in a single dose.
16. The method of claim 11 wherein the dose is administered in multiple doses per day.
17. The method of claim 11 wherein the pharmaceutical composition is a capsule or tablet.
18. The method of claim 17 wherein the capsule or tablet comprises about 0.1 mg/kg/day to about 10 mg/kg/day of the compound or a pharmaceutically acceptable salt thereof.
19. The method of claim 17 wherein the total daily dose is about 0.2 mg/kg/day to about 5 mg/kg/day.
20. The method of claim 17 wherein the pharmaceutical composition is administered orally.