Neuropharmacological treatment of sleep-related breathing disorders

• US 20030236228A1
• Filed: 03/27/2003
• Published: 12/25/2003
• Est. Priority Date: 03/04/1999
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Radulovacki, Miodrag, Carley, David W.
• Granted Patent: US 6,974,814 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/13 Amines A61K31/04 takes precedence
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/28 Compounds containing heavy metals
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4015 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4465 only substituted in position 4
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 31/675 : having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/69 : Boron compounds
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system

Abstract

The present invention relates generally to pharmacological methods for the prevention or amelioration of sleep-related breathing disorders via administration of agents or combinations of agents that possess glutamate-related and/or glycine-related pharmacological activity or that modulate the release of glutamate, glycine, or both from nerve terminals with the central nervous system.

Claims

1. A method of preventing or ameliorating sleep-related breathing disorder the method comprising administering to a patient in need thereof an effective amount of a glutamate receptor antagonist wherein the effects of the antagonist are exerted only in the central nervous system.

2. The method of claim 1 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

3. The method of claim 1 or claim 2 wherein the glutamate receptor antagonist is selected from the group consisting of D-AP5, CGS19755, CGP37849, LY233053, AIDA, (s)-(+)-CBPG, CPCCOEt, EGLU, LY307452, LY341495, PCCG-4, 4CPG, memantine, and amantadine

4. A method of preventing or ameliorating sleep-related breathing disorder the method comprising administering to a patient in need thereof an effective amount of a glycine receptor antagonist wherein the effects of the antagonist are exerted only in the central nervous system.

5. The method of claim 4 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

6. The method of claim 4 or claim 5 wherein the glycine receptor antagonist is selected from the group consisting of 5,7-dichlorokynurenate, L689560, MNQX, picrotoxin, and cyanotriphenylborate.

7. A method of preventing or ameliorating sleep-related breathing disorders the method comprising administering to a patient in need thereof an effective amount of an agent or combination of agents having both glutamate receptor antagonistic activity and glycine antagonistic activity within the central nervous system.

8. The method of claim 7 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

9. A method of preventing or ameliorating sleep-related breathing disorders the method comprising administering to a patient in need thereof an effective amount of an agent or combination of agents that inhibit the release of glutamate from nerve terminals within the central nervous system.

10. The method of claim 9 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

11. A method of preventing or ameliorating sleep-related breathing disorders the method comprising administering to a patient in need thereof an effective amount of an agent or combination of agents that inhibit the release of glycine from nerve terminals within the central nervous system.

12. The method of claim 11 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

14. The method of claim 12 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

13. A method of preventing or ameliorating sleep-related breathing disorders the method comprising administering to a patient in need thereof an effective amount of an agent or combination of agents having the ability to prevent the release of both glutamate and glycine activity within the central nervous system.

15. A method of preventing or ameliorating sleep-related breathing disorders the method comprising administering to a patient in need thereof an effective amount of an agent or combination of agents having agonistic activity at presynaptic inhibitory receptors located on glutamergic and/or glycinergic nerve terminals within the central nervous system.

16. The method of claim 15 wherein the sleep-related breathing disorder is selected from the group consisting of obstructive sleep apnea syndrome, apnea of prematurity, congenital central hypoventilation syndrome, obesity hypoventilation syndrome, central sleep apnea syndrome, Cheyne-Stokes respiration, and snoring.

17. The method of claim 16 or claim 17 wherein the agent or combination of agents are GABA receptor agonists.

18. The method of claim 17 wherein the GABA receptor agonists are selected from the group consisting of isoguvacine, muscimol, THIP, piperidine-4-sulphonic acid, flunitrazepam, zolpidem, abecarnil, ZK93423, L-baclofen, CGP27492, piracetam, progabide, and CGP35024.