Uses of combinations (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine in methods of treating movement disorder
The invention relates to pharmaceutical compositions containing both (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine and their therapeutic uses, for example in the treatment of movement disorders, such as Tourette's syndrome.
1. A pharmaceutical unit dosage form comprising a combination of (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine, or pharmaceutically acceptable salts thereof, and a pharmaceutically acceptable excipient, wherein the combination of (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine is a scalemic mixture, wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.1:1 to 20:1.
2. A pharmaceutical unit dosage form according to claim 1 , wherein the combination of (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine is unaccompanied by any other isomers of dihydrotetrabenazine.
3. A pharmaceutical unit dosage form according to claim 1 wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 20:1.
4. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.1:1 to 15:1.
5. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-a-dihydrotetrabenazine is from 1.1:1 to 10:1.
6. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.1:1 to 5:1.
7. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.1:1 to 4:1.
8. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.1:1 to 3:1.
9. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 15:1.
10. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 10:1.
11. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 5:1.
12. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 4:1.
13. A pharmaceutical unit dosage form according to claim 1 , wherein the ratio of (+)-α-dihydrotetrabenazine to (−)-α-dihydrotetrabenazine is from 1.2:1 to 3:1.
14. A method of treating a movement disorder in a subject in need thereof, the method comprising administering to the subject the pharmaceutical unit dosage form according to claim 1 .
15. A method according to claim 14 , wherein the method comprises administering to a subject in need thereof an effective therapeutic amount of the pharmaceutical unit dosage form sufficient to provide a dosage of from 1 mg to 20 mg of (+)-α-dihydrotetrabenazine per day.
16. A method according to claim 14 , wherein the method comprises administering to a subject an amount of the pharmaceutical unit dosage form of from 0.01 mg/kg to 0.3 mg/kg per day provided that the total amount of (+)-α-dihydrotetrabenazine administered per day is in the range from 1 mg to 20 mg.
17. A method according to claim 14 , wherein the movement disorder is a hyperkinetic movement disorder selected from Huntington's disease, hemiballismus, senile chorea, tic disorders, tardive dyskinesia, dystonia and Tourette's syndrome.
18. A method according to claim 14 , wherein the movement disorder is Tourette's syndrome.
19. A method according to claim 14 , wherein the method comprises administering to a subject an amount of the pharmaceutical unit dosage form sufficient to cause a level of blocking of from 20% to 90% of VMAT2 proteins in the subject.
20. A method according to claim 14 , wherein the combination of (+)-α-dihydrotetrabenazine and (−)-α-dihydrotetrabenazine is unaccompanied by any other isomers of dihydrotetrabenazine.
21. A method according to claim 14 , wherein the subject is a human subject.