Administration and dosage of diaminophenothiazines
The invention provides novel regimens for treatment of neurodegenerative disorders utilising methylthioninium (MT)-containing compounds. The regimens are based on novel findings in relation to the dosage of MT compounds, and their interaction with symptomatic treatments based on modulation of acetylcholinesterase levels.
1. A method of therapeutic treatment of mild cognitive impairment in a subject,
which method comprises orally administering to said subject a methylthioninium (MT)-containing compound,
wherein said administration provides a total daily dose of between 0.5 and 20 mg of MT to the subject per day,
wherein the MT-containing compound is LMTM:
2. The method as claimed in claim 1 , wherein the total daily dose of MT is 2 to 15 mg.
3. The method as claimed in claim 1 , wherein said therapeutic treatment with the MT-containing compound comprises a total daily dose of LMTM of 0.8 to 33 mg/day.
4. The method as claimed in claim 1 , wherein said therapeutic treatment with the MT-containing compound comprises a dose of LMTM of 9 mg/once per day.
5. A method of prophylactic treatment of mild cognitive impairment in a subject,
which method comprises orally administering to said subject a methylthioninium (MT)-containing compound,
wherein said administration provides a total daily dose of between 0.5 and 20 mg of MT to the subject per day,
wherein the MT-containing compound is LMTM:
6. The method as claimed in claim 1 , wherein the subject has not historically received treatment with an acetylcholinesterase inhibitor or an N-methyl-D-aspartate receptor antagonist.
7. The method as claimed in claim 1 , wherein the subject has historically received treatment with an acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist, but ceased that medication at least 1, 2, 3, 4, 5, 6, 7, or 8 weeks prior to treatment with the MT containing compound.
8. The method as claimed in claim 1 , wherein the subject is selected as one who is receiving treatment with an acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist,
wherein said treatment with the acetylcholinesterase inhibitor and\or an N-methyl-D-aspartate receptor antagonist is discontinued prior to treatment with the MT-containing compound.
9. The method as claimed in claim 1 , wherein said therapeutic treatment comprises a total daily dose of the MT-containing compound administered once per day.
10. The method as claimed in claim 1 , wherein said therapeutic treatment comprises a total daily dose of the MT-containing compound administered as a split dose twice per day.
11. The method as claimed in claim 1 , wherein said therapeutic treatment comprises a total daily dose of the MT-containing compound administered as a split dose three times per day.
12. The method as claimed in claim 5 , wherein said prophylactic treatment comprises a total daily dose of the MT-containing compound administered once per day.
13. The method as claimed in claim 5 , wherein said prophylactic treatment comprises a total daily dose of the MT-containing compound administered as a split dose twice per day.
14. The method as claimed in claim 5 , wherein said prophylactic treatment comprises a total daily dose of the MT-containing compound administered as a split dose three times per day.
15. The method as claimed in claim 2 , wherein the total daily dose of MT is 3 to 10 mg.
16. The method as claimed in claim 3 , wherein the total daily dose of LMTM is 6 to 12 mg/day.