Pharmacological treatment for sleep apnea

• US 6,727,242 B2
• Filed: 12/14/2001
• Issued: 04/27/2004
• Est. Priority Date: 02/27/1998
• Status: Expired due to Fees

• Current Assignee: N.V. Organon (Merck & Co., Inc.)
• Original Assignee: Board of Trustees of The University of Illinois
• Inventors: Radulovacki, Miodrag, Carley, David W.
• Primary Examiner(s): Jones, Dwayne C.
• Assistant Examiner(s): JAGOE, DONNA A
• Application Number:
  US10/016,901
• Publication Number:
  US 20020086870A1
• Time in Patent Office: 865 Days
• Field of Search: 514/397, 514/649, 514/321, 514/415, 514/252.15, 514/252.18, 514/252.19
• US Class Current: 514/214.02
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/451 having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
• CPC Class Codes: A61K 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/16 : Central respiratory analeptics
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates generally to pharmacological methods for the prevention of amelioration of sleep-related breathing disorders via administration of agents or combinations of agents that possess serotonin-related pharmacological activity.

Claims

1. A method of ameliorating a sleep-related breathing disorder comprising administering to a patient in need thereof an effective amount of ondansetron.

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. A method of ameliorating a sleep-related breathing disorder comprising administering to a patient in need thereof an effective amount of a composition comprising ondansetron and a serotonin receptor agonist.

4. The method of claim 3 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.

5. The method of claim 3 wherein the serotonin receptor agonist is selected from the group consisting of 8-OH-DPAT, sumatriptan, L694247, buspirone, alnitidan, zalospirone, ipsapirone, gepirone, zolmitriptan, risatriptan, 311C90, α

-Me-5-HT, BW723C86, and MCPP.

6. The method of claim 3 wherein the serotonin receptor agonist is a 5-hydroxytryptamine₁ receptor subtype agonist.

7. The method of claim 3 wherein the serotonin receptor agonist is a 5-hydroxytryptamine₂ receptor subtype agonist.

8. The method of claim 3 wherein the effects of the serotonin receptor agonist are exerted in the central nervous system.

9. The method of claim 3 wherein the effects of ondansetron are exerted in the peripheral nervous system.

10. The method of claim 3 wherein the effects of the serotonin receptor agonist are exerted in the central nervous system and wherein the effects of ondansetron are exerted in the peripheral nervous system.

11. A method of ameliorating a sleep-related breathing disorder comprising administering to a patient in need thereof an effective amount of a serotonin receptor antagonist and an effective amount of a selective serotonin reuptake inhibitor.

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

13. The method of claim 11 wherein the serotonin receptor antagonist is selected from the group consisting of ketanserin, cinanserin, LY-53,857j, metergoline, LY-278,584, methiothepin, p-NPPL, NAN-190, piperazine, SB-206553, SDZ-205,557j, 3-tropanyl-indole-3-carboxylate, 3-tropanyl-indole-3-carboxylate methiodide, methysergide, risperidone, cyproheptadine, clozapine, mianserin, ritanserin, granisetron, and ondansetron.

14. The method of claim 11 wherein the selective serotonin reuptake inhibitor is selected from the group consisting of fluoxetine and paroxetine.