Phenothiazine compounds for treating mild cognitive impairment

1. A method for the symptomatic treatment of memory loss in a patient suffering from amnestic mild cognitive impairment (MCI) with no evidence of tau pathology, wherein the patient has a Mini-Mental State Examination Score of 25, 26, 27, 28 or 29 and is not diagnosed with Alzheimer's disease,

which method comprises administering an effective amount of a diaminophenothiazine compound to said patient,

wherein said compound is selected from compounds of the following formulae:

wherein each one of R 1 , R 2 , R 4 , R 6 , R 8 , and R 9 is —H;

and wherein, in each group —NR 3NA R 3NA each one of R 3NA and R 3NB is independently selected from: —H; and unsubstituted aliphatic C 1-6 alkyl

and wherein, in each group —NR 7NA R 7NA , each one of R 7NA and R 7NB is independently selected from: —H; and -unsubstituted aliphatic C 1-6 alkyl;

and wherein R N10 , if present, is —H;

and wherein X − , if present, is one or more anionic counter ions to achieve electrical neutrality,

and pharmaceutically acceptable salts, mixed salts, and hydrates thereof.

2. The method of claim 1 , wherein, in each group —NR 3NA R 3NB , each one of R 3NA and R 3NB is independently selected from: —H, -Me, -Et, -nPr, and -iPr.

3. The method of claim 1 , wherein, in each group —NR 3NA R 3NB , each one of R 3NA and R 3NB is independently selected from: —H and -Me.

4. The method of claim 1 , wherein, in each group —NR 7NA R 7NB , each one of R 7NA and R 7NB is independently selected from: —H, -Me, -Et, -nPr, and -iPr.

5. The method of claim 1 , wherein, in each group —NR 7NA R 7NB , each one of R 7NA and R 7NB is independently selected from: —H and -Me.

6. The method of claim 1 , wherein R N10 is present.

7. The method of claim 1 , wherein X − , if present, is selected from Cl − , or Br − .

8. The method of claim 1 , wherein the compound is selected from the group consisting of any of the following compounds A, B, G, H, M, N, P and Q, and pharmaceutically acceptable salts, mixed salts, and hydrates thereof:

A

MTC

methyl-thioninium chloride

B

ETC

ethyl-thioninium chloride

G

MTZ

methyl-thioninium chloride zinc chloride mixed salt

H

ETZ

ethyl-thioninium chloride zinc chloride mixed salt

M

MTN

methyl-thioninium nitrate

N

ETN

ethyl-thioninium nitrate

P

Thionine

Q

9. The method of claim 8 , wherein the compound is

10. The method of claim 8 , wherein the compound is

11. The method of claim 1 wherein said treatment comprises administering said diaminophenothizine compound in combination with a cholinergic drug that enhances or mimics the action of acetylcholine.

12. The method of claim 1 wherein said patient does not suffer from a defect in mitochondrial energy metabolism.

13. The method of claim 1 wherein less than or equal to 400, 300, 200, 100, 50, 40, 30, 20, 15, or 10 mg daily total dose is administered.

14. The method of claim 1 wherein less than 50% of the total amount of diaminophenothiazine compound in the medicament is either a compound of formula (I) or a pharmaceutically acceptable salt, mixed salt, or hydrate thereof.