TREATMENT OF COGNITIVE DISORDERS WITH CERTAIN ALPHA-7 NICOTINIC ACID RECEPTORS IN COMBINATION WITH ACETYLCHOLINESTERASE INHIBITORS
A method for improving cognition comprising administering to a patient (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and an acetylcholinesterase inhibitor is described together with related compositions.
1 . A method for improving cognition comprising administering to a patient (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and an acetylcholinesterase inhibitor.
2 . The method of claim 1 wherein the patient has been diagnosed with Alzheimer's disease or pre-Alzheimer's disease.
3 . The method of claim 1 wherein the patient has been diagnosed with mild to moderate Alzheimer's disease.
4 . The method of claim 1 wherein the patient has been diagnosed with moderate to severe Alzheimer's disease.
5 . The method of any of the forgoing claims wherein the acetylcholinesterase inhibitor is selected from tacrine, donepezil, rivastigmine and galantamine.
6 . The method of claim 5 wherein the acetylcholinesterase inhibitor is selected from donepezil, rivastigmine and galantamine.
7 . The method of claim 5 wherein the acetylcholinesterase inhibitor is selected from donepezil and rivastigmine.
8 . The method of any of the forgoing claims wherein the patient has been administered an acetylcholinesterase inhibitor for a period of time prior to being administered (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof.
9 . The method of claim 8 wherein the prior administration has been for at least one month.
10 . The method of claim 9 wherein the prior administration has been for at least three months.
11 . The method of claim 10 wherein the prior administration has been for at least six months.
12 . The method of any of the forgoing claims wherein the method improves one or more of: learning, delayed memory, attention, working memory, visual learning, speed of processing, vigilance, verbal learning, visual motor function, social cognition, long term memory or executive function.
13 . The method of claim 1 wherein one or both of the (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and the acetylcholinesterase inhibitor is administered at a subclinical dose.
14 . The method of claim 13 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at less than 1.0 mg/day.
15 . The method of claim 13 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at less than 0.5 mg/day.
16 . The method of claim 13 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at less than 0.3 mg/day.
17 . The method of claim 13 wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof is orally administered at less than 0.1 mg/day.
18 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered at less than 5 mg/day.
19 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered 4.5 mg/day or less.
20 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered at 4.0 mg/day or less.
21 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered at 2.5 mg/day or less.
22 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered at 1.5 mg/day or less.
23 . The method of claim 13 wherein the acetylcholinesterase inhibitor is donepezil and is orally administered at than 1.0 mg/day or less.
24 . The method of claim 1 wherein the acetylcholinesterase inhibitor is administered at a dose that achieves 10-65% steady state red blood cell acetylcholinesterase inhibition.
25 . A pharmaceutical composition comprising (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and an acetylcholinesterase inhibitor.
26 . The pharmaceutical composition of claim 25 wherein the acetylcholinesterase inhibitor is selected from tacrine, donepezil, rivastigmine and galantamine.
27 . The pharmaceutical composition of claim 25 wherein the acetylcholinesterase inhibitor is selected from donepezil, rivastigmine and galantamine.
28 . The pharmaceutical composition of claim 25 wherein the acetylcholinesterase inhibitor is selected from donepezil and rivastigmine.
29 . The pharmaceutical composition of claim 25 wherein the acetylcholinesterase inhibitor is donepezil.
30 . A daily unit dosage pharmaceutical composition comprising no more than 1.0 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof, an acetylcholinesterase inhibitor and a pharmaceutically acceptable carrier.
31 . The daily unit dosage pharmaceutical composition of claim 30 comprising no more than 0.5 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof.
32 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 0.3 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof.
33 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 0.1 mg of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof.
34 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 5 mg of donepezil.
35 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 4 mg of donepezil.
36 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 2.5 mg of donepezil.
37 . The daily unit dosage pharmaceutical composition of claim 31 comprising no more than 1 mg of donepezil.
38 . Packaged pharmaceuticals comprising a package containing a first unit dosage pharmaceutical composition comprising (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide or a pharmaceutically acceptable salt thereof and a second unit dosage pharmaceutical composition comprising an acetylcholinesterase inhibitor.