Use of nicotinic acetylcholine receptor alpha 7 activators
The invention concerns the use of a nicotinic acetylcholine receptor alpha 7 activators for the treatment, prevention or delay of progression of dyskinesia associated with dopamine agonist therapy in Parkinson's Disease.
1 . In a method of treating a Parkinson's Disease patient with a dopamine agonist therapy, the improvement comprising:
administering to the Parkinson's Disease patient a therapeutically effective amount of (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form.
2 . The improvement of claim 1 , wherein administering the therapeutically effective amount of (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form to the Parkinson's Disease patient results in:
a reduction in a scale of involuntary movements, a reduction in a number of involuntary movements, an improvement in ability to carry out normal tasks, an improved ability to walk, or an increased period of time between episodes of dyskinesia experienced by the Parkinson's Disease patient.
3 . The improvement of claim 1 , wherein the dopamine agonist therapy comprises levodopa.
4 . The improvement of claim 3 , wherein the levodopa is administered to the Parkinson's Disease patient in an amount that is reduced by at least 10% relative to a daily dosage of 250-1500 mg/day that would be effective for treating a Parkinson's Disease patient not being administered the (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form.
5 . The improvement of claim 4 , wherein the levodopa is administered to the Parkinson's Disease patient in an amount that is reduced by at least 20% relative to a daily dosage of 250-1500 mg/day that would be effective for treating a Parkinson's Disease patient not being administered the (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form.
6 . The improvement of claim 3 , wherein the dopamine agonist therapy further comprises a levodopa decarboxylase inhibitor in combination with the levodopa.
7 . The improvement of claim 6 , wherein the levodopa decarboxylase inhibitor comprises one or both of carbidopa or benserazide.
8 . The improvement of claim 3 , wherein the dopamine agonist therapy further comprises a catechol-O-methyl transferase inhibitor, in combination with the levodopa.
9 . The improvement of claim 8 , wherein the catechol-O-methyl transferase inhibitor comprises one or both of tolcapone or entacapone.
10 . The improvement of claim 1 , wherein the dopamine agonist therapy comprises a monoamine oxidase B-inhibitor.
11 . The improvement of claim 10 , wherein the monoamine oxidase B-inhibitor comprises one or both of selegiline or rasagiline.
12 . The improvement of claim 1 , wherein the dopamine agonist therapy comprises a dopamine receptor agonist selected from a group consisting of: bromocriptine, pergolide, pramipexole, ropinirole, cabergoline, apomorphine, and lisuride.
13 . The improvement of claim 1 , wherein the therapeutically effective amount of (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form comprises from about 3 mg/day to about 100 mg/day.
14 . The improvement of claim 1 , wherein the therapeutically effective amount of (R)-3-(6-p-tolyl-pyridin-3-yloxy)-1-aza-bicyclo[2.2.2]octane in free base form or in acid addition salt form comprises from about 2.5 mg/day to about 25 mg/day.