Treatment of sleep disorders with cholinesterase inhibitors

• US 20050038013A1
• Filed: 08/11/2004
• Published: 02/17/2005
• Est. Priority Date: 08/13/2003
• Status: Active Grant

• Current Assignee: Michael Gold
• Original Assignee: Michael Gold
• Inventors: Gold, Michael
• Granted Patent: US 7,297,691 B2
• Time in Patent Office: Days
• US Class Current: 514/214.30
• CPC Class Codes: A61K 31/27 of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
• CPC Class Codes: A61K 31/366 having six-membered rings, e.g. delta-lactones
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/4406 only substituted in position 3, e.g. zimeldine nicotinic acid A61K31/455
• CPC Class Codes: A61K 31/4706 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is concerned with treatment of sleep disorders by administering a cholinesterase inhibitor, and in particular, by administering galantamine or a pharmaceutically acceptable salt thereof. Also in particular, cholinesterase inhibitors that are active at nicotinic receptors and that are selective for acetylcholinesterase over butylcholinesterase are used in treating sleep disorders.

Claims

1. A method for the treatment of a sleep disorder, comprising administering, to a patient in need thereof, an effective amount of a pharmaceutically acceptable cholinesterase inhibitor or a prodrug therefor.

2. A method according to claim 1 wherein the sleep disorder is selected from the group consisting of an intrinsic sleep disorder, an extrinsic sleep disorder and a circadian rhythm sleep disorder.

3. A method according to claim 1 wherein the sleep disorder is selected from the group consisting of Psychophysiological Insomnia, Sleep State Misperception, Idiopathic Insomnia, Narcolepsy, Recurrent Hypersomnia, Idiopathic Hypersomnia, Posttraumatic Hypersomnia, Obstructive Sleep Apnea Syndrome, Central Sleep Apnea Syndrome, Central Alveolar Hypoventilation Syndrome, Periodic Limb Movement Disorder, Restles Legs Syndrome Intrinsic Sleep Disorder NOS, Inadequate Sleep Hygiene, Environmental Sleep Disorder, Altitude Insomnia, Adjustment Sleep Disorder, Insufficient Sleep Syndrome, Limit-Setting Sleep Disorder, Sleep-Onset Association Disorder, Food Allergy Insomnia, Nocturnal Eating (Drinking) Syndrome, Hypnotic-Dependent Sleep Disorder, Stimulant-Dependent Sleep Disorder, Toxin-Induced Sleep Disorder, Extrinsic Sleep Disorder NOS, Time Zone Change (Jet Lag) Syndrome, Shift Work Sleep Disorder, Irregular Sleep-Wake Pattern, Delayed Sleep Phase Syndrome, Advanced Sleep Phase Syndrome, Non-24-Hour Sleep-Wake Disorder, and Circadian Rhythm Sleep Disorder NOS.

4. A method according to claim 1, wherein the cholinesterase inhibitor is selected from the group consisting of galantamine and galantamine derivatives, norgalantamine and norgalantamine derivatives, epigalantamine and epigalantamine derivatives, physostigmine, tacrine and tacrine analogues, fasciculin, metrifonate, heptyl-physostigmine, norpyridostigmine, norneostigmine, and huperzine, or a prodrug therefor.

5. A method according to claim 1, in which the cholinesterase inhibitor is an acetylcholinesterase inhibitor which is active substantially selectively at nicotinic receptor sites.

6. A method according to claim 1, in which the acetylcholinesterase inhibitor is one which has an at least 10-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase.

7. A method according to claim 5, in which the acetylcholinesterase inhibitor is one which has an at least 20-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase.

8. A method according to claim 5, in which the acetylcholinesterase inhibitor is one which has an at least 40-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase.

9. A method according to claim 5, in which the acetylcholinesterase inhibitor is one which, upon administration in an amount of 10 mg to a healthy adult, results in inhibition of at least 40% of the acetylcholinesterase activity in erythrocytes from the adult and no substantial inhibition of butyrylcholinesterase therein.

10. A method according to claim 9, in which the acetylcholinesterase inhibitor is one which, when administered in an amount of 10 mg to an adult, results in inhibition of at least 50% of the acetylcholinesterase activity in erythrocytes from the adult.

11. A method according to claim 1, in which the cholinesterase inhibitor is one which is capable of passing the blood-brain barrier in humans.

12. A method according to claim 1, in which the cholinesterase inhibitor is one which, upon administration to a human, increases the cortisol level in the human.

13. A method according to claim 1, in which the cholinesterase inhibitor is galantamine or a salt, derivative or functional equivalent thereof.

14. A method according to claim 13, in which the functional equivalent is a compound which is an acetylcholinesterase capable of passing the blood brain barrier, which has an at least 10-fold selectivity for acetylcholinesterase as opposed to butyrylcholinesterase.

25. A method according to claim 1, in which the cholinesterase inhibitor is administered orally in a dosage which is equipotent with 5-2000 mg galantamine hydrobromide per day.

26. A method according to claim 25, in which the cholinesterase inhibitor is administered at a dosage which is equipotent with 10-500 mg galantamine hydrobromide per day.

27. A method according to claim 26, in which the cholinesterase inhibitor is administered at a dosage which is equipotent with 10-50 mg, such as 10-30 mg, of galantamine hydrobromide per day.

15. A method for the treatment of a sleep disorder, comprising administering, to a patient in need thereof, an effective amount of a galantamine or a galantamine salt or a galantamine derivative.

16. A method according to claim 15, in which the compound is a galantamine derivative of the general formula II

17. A method according to claim 15, in which the compound is galantamine or a derivative of galantamine and has the formula I

18. A method according to claim 15, wherein the galantamine salt is galantamine hydrobromide.

19. A method according to claim 15, wherein the sleep disorder is selected from the group consisting of Psychophysiological Insomnia, Sleep State Misperception, Idiopathic Insomnia, Narcolepsy, Recurrent Hypersomnia, Idiopathic Hypersomnia, Posttraumatic Hypersomnia, Obstructive Sleep Apnea Syndrome, Central Sleep Apnea Syndrome, Central Alveolar Hypoventilation Syndrome, Periodic Limb Movement Disorder, Restles Legs Syndrome Intrinsic Sleep Disorder NOS, Inadequate Sleep Hygiene, Environmental Sleep Disorder, Altitude Insomnia, Adjustment Sleep Disorder, Insufficient Sleep Syndrome, Limit-Setting Sleep Disorder, Sleep-Onset Association Disorder, Food Allergy Insomnia, Nocturnal Eating (Drinking) Syndrome, Hypnotic-Dependent Sleep Disorder, Stimulant-Dependent Sleep Disorder, Toxin-Induced Sleep Disorder, Extrinsic Sleep Disorder NOS, Time Zone Change (Jet Lag) Syndrome, Shift Work Sleep Disorder, Irregular Sleep-Wake Pattern, Delayed Sleep Phase Syndrome, Advanced Sleep Phase Syndrome, Non-24-Hour Sleep-Wake Disorder, and Circadian Rhythm Sleep Disorder NOS.

20. A method according to claim 15, wherein the galantamine derivative is one which is able to cross the blood brain barrier in humans.

21. A method according to claim 15, wherein the cholinesterase inhibitor or the galantamine or the galantamine salt or the galantamine derivative is administered in the form of a pharmaceutical composition which is a tablet, a capsule, a sustained release capsule comprising micro capsules of the active ingredient, a solution or suspension, a plaster for transdermal application, or a suppository.

22. A method according to claim 15, in which the cholinesterase inhibitor or the galantamine or the galantamine salt or the galantamine derivative is administered perenterally at a dosage which is equipotent with 0.1-1,000 mg of galantamine hydrobromide per day, such as 5-1,000 mg of galantamine hydrobromide.

23. A method according to claim 22, in which the cholinesterase inhibitor is administered in a dosage which is equipotent with to 10-500 mg galantamine hydrobromide per day, such as 50-300 mg per day.

24. A method according to claim 22, in which the cholinesterase inhibitor is administered in a dosage which is equipotent with 10-50, in particular 10-30, mg galantamine hydrobromide per day.