Method of treating Tourette'S disorder with GABA-aminotransferase inactivators
View Patent ↗The present invention is a method of treating Tourette's Disorder (TD) using GABA ergic drugs that elevate the amount of stored presynaptic GABA and do not significantly increase GABA tone (a continuous background level of GABA signaling) in the brain. The administration of vigabatrin and/or (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid hydrochloride salt is expressly contemplated.
1. A method of treating Tourettes Disorder (TD) comprising elevating the build-up of GABA in presynaptic terminals of GABA-ergic neurons.
2. The method of claim 1 wherein the GABA levels are elevated by administration of an effective amount of vigabatrin or (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid, or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 wherein the salt is selected from the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate, pamoate, amino acids, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, or diethanolamine salts.
4. A method of treating Tourette's Disorder (TD) comprising elevating the GABA in presynaptic terminals of GABA-ergic neurons without significantly elevating the background level of GABA in the brain.
5. The method of claim 4 wherein the GABA levels are elevated by administration of an effective amount of vigabatrin or (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid, or a pharmaceutically acceptable salt thereof.
6. The method of claim 5 wherein the salt is selected from the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate, pamoate, amino acids, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, or diethanolamine salts.
7. A method of treating Tourette's Disorder (TD) comprising the administration of an effective amount of a GABA-aminotransferase inactivator.
8. The method of claim 7 wherein the GABA-aminotransferase inactivator is selected from vigabatrin or (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid.
9. The method of claim 7 wherein the GABA-aminotransferase inactivator is vigabatrin or a pharmaceutically acceptable salt thereof.
10. The method of claim 9 wherein the salt is a hydrochloride salt.
11. The method of claim 9 wherein the salt is selected from the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate, pamoate, amino acids, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, or diethanolamine salts.
12. The method of claim 9 wherein the vigabatrin is administered daily at a dose between 0.5 and 4 grams.
13. The method of claim 9 wherein the vigabatrin is administered at 1 gram/day for the first week, 2 grams/day for the second week, administered at 3 grams/day for the third, fourth, fifth, sixth, and seventh weeks, 2 grams/day for the eighth week, and 1 gram/day for the ninth week of treatment.
14. The method of claim 8 wherein the GABA-aminotransferase inactivator is (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid or a pharmaceutically acceptable salt thereof.
15. The method of claim 14 wherein the salt is a hydrochloride salt.
16. The method of claim 14 wherein the salt is selected from the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate, pamoate, amino acids, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, or diethanolamine salts.
17. The method of claim 14 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered daily at a dose between 0.7 and 1000 milligrams.
18. The method of claim 14 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 25 milligrams/day for the first week, 150 milligrams/day for the second week, administered at 500 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 150 milligrams/day for the ninth week of treatment.
19. The method of claim 14 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 5 milligrams/day for the first week, 10 milligrams/day for the second week, administered at 25 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 10 milligrams/day for the ninth week of treatment.
20. The method of claim 14 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 25 milligrams/day for 9 consecutive weeks.
21. The method of claim 14 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 10 milligrams/day for 9 consecutive weeks.
22. A method of treating Tourette's Disorder (TD) comprising the administration of an effective amount of vigabatrin.
23. The method of claim 22 wherein the vigabatrin is administered daily at a dose between 0.25 and 4 grams.
24. The method of claim 22 wherein the vigabatrin is administered at 1 gram/day for the first week, 2 grams/day for the second week, administered at 3 grams/day for the third, fourth, fifth, sixth, and seventh weeks, 2 grams/day for the eighth week, and 1 gram/day for the ninth week of treatment.
25. A method of treating Tourette's comprising the administration of an effective amount of (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid or a pharmaceutically acceptable salt thereof.
26. The method of claim 25 wherein the salt is a hydrochloride salt.
27. The method of claim 25 wherein the salt is selected from the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p-toluenesulfonate, pamoate, amino acids, aluminum, calcium, lithium, magnesium, potassium, sodium, zinc, or diethanolamine salts.
28. The method of claim 25 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered daily at a dose between 0.7 and 1000 milligrams.
29. The method of claim 26 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid hydrochloride salt is administered daily at a dose between 0.7 and 1000 milligrams.
30. The method of claim 25 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 25 milligrams/day for the first week, 150 milligrams/day for the second week, administered at 500 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 150 milligrams/day for the ninth week of treatment.
31. The method of claim 26 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid hydrochloride salt is administered at 25 milligrams/day for the first week, 150 milligrams/day for the second week, administered at 500 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 150 milligrams/day for the ninth week of treatment.
32. The method of claim 25 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 5 milligrams/day for the first week, 10 milligrams/day for the second week, administered at 25 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 10 milligrams/day for the ninth week of treatment.
33. The method of claim 26 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid hydrochloride salt is administered at 5 milligrams/day for the first week, 10 milligrams/day for the second week, administered at 25 milligrams/day for the third, fourth, fifth, sixth, seventh, and eighth weeks, and 10 milligrams/day for the ninth week of treatment.
34. The method of claim 25 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 25 milligrams/day for 9 consecutive weeks.
35. The method of claim 25 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid is administered at 10 milligrams/day for 9 consecutive weeks.
36. The method of claim 26 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid hydrochloride salt is administered at 25 milligrams/day for 9 consecutive weeks.
37. The method of claim 26 wherein the (1S,3S)-3-amino-4-methylenyl-1-cyclopentanoic acid hydrochloride salt is administered at 10 milligrams/day for 9 consecutive weeks.