Treatment of conditions through pharmacological modulation of the autonomic nervous system

• US 20050143378A1
• Filed: 12/29/2003
• Published: 06/30/2005
• Est. Priority Date: 12/29/2003
• Status: Abandoned Application

• Current Assignee: Palo Alto Investors
• Original Assignee: Palo Alto Investors
• Inventors: Lee, Patrick Yuarn-Bor, Yun, Anthony Joonkyoo
• Application Number:
  US10/748,897
• Publication Number:
  US 20050143378A1
• Time in Patent Office: Days
• US Class Current: 514/235.500
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/166 having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
• 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 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/255 of sulfoxy acids or sulfur analogues thereof
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61N 1/36007 of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/3606 adapted for a particular treatment
• CPC Class Codes: A61N 1/36062 Spinal stimulation
• CPC Class Codes: A61N 1/36071 Pain
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: G16H 20/10 : relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Methods are provided for treating a subject for a condition caused by an abnormality in the subject'"'"'s autonomic nervous system. In accordance with the subject methods, at least a portion of a subject'"'"'s autonomic nervous system is pharmacologically modulated with at least one beta-blocker in a manner that is effective to treat the subject for the condition. The subject methods find use in the treatment of a variety of different conditions, where such conditions include various disease conditions. Also provided are systems and kits for use in practicing the subject methods.

Claims

1. A method of treating a subject for a condition caused by an autonomic nervous system abnormality comprising modulating at least a portion of said subject'"'"'s autonomic nervous system by administering an effective amount of at least one beta-blocker to said subject to treat said subject for at least one of:

neurodegenerative conditions;

neuroinflammatory conditions;

orthopedic inflammatory conditions;

lymphoproliferative conditions;

autoimmune conditions;

inflammatory conditions;

infectious diseases, pulmonary conditions;

transplant-related conditions, gastrointestinal conditions;

endocrine conditions;

genitourinary conditions selected from the group of renal failure, hyperreninemia, hepatorenal syndrome and pulmonary renal syndrome;

aging associated conditions;

neurologic conditions;

Th-2 dominant conditions;

conditions that cause hypoxia;

conditions that cause hypercarbia;

conditions that cause hypercapnia;

conditions that cause acidosis;

conditions that cause academia, pediatric-related conditions;

OB-GYN conditions, sudden death syndromes, fibrosis;

post-operative recovery conditions;

post-procedural recovery conditions;

chronic pain;

disorders of thermoregulation, cyclic vomiting syndrome and trauma.

2. The method according to claim 1, wherein said modulation results in a sympathetic bias in at least a portion of said autonomic nervous system.

3. The method of claim 2, wherein said abnormality is characterized by a sympathetic bias.

4. The method of claim 2, wherein said abnormality is characterized by a parasympathetic bias.

5. The method according to claim 1, wherein said modulation results in a parasympathetic bias in at least a portion of said autonomic nervous system.

6. The method of claim 5, wherein said abnormality is characterized by a sympathetic bias.

7. The method of claim 5, wherein said abnormality is characterized by a parasympathetic bias.

8. The method according to claim 1, wherein said modulating results in a substantially equal parasympathetic and sympathetic functions in at least a portion of said autonomic nervous system.

9. The method of claim 8, wherein said abnormality is characterized by a sympathetic bias.

10. The method of claim 8, wherein said abnormality is characterized by a parasympathetic bias.

11. The method of claim 1, wherein said abnormality is characterized by an abnormally high parasympathetic activity.

12. The method of claim 11, wherein said abnormality is characterized by an abnormally low sympathetic activity.

13. The method of claim 11, wherein said abnormality is characterized by normal sympathetic activity.

14. The method of claim 11, wherein said abnormality is characterized by an abnormally high sympathetic activity.

15. The method of claim 11, further comprising decreasing said abnormally high parasympathetic activity.

16. The method of claim 1, wherein said abnormality comprises an abnormally low parasympathetic activity.

17. The method of claim 16, wherein said abnormality comprises an abnormally low sympathetic activity.

18. The method of claim 16, wherein said abnormality comprises normal sympathetic activity.

19. The method of claim 16, wherein said abnormality comprises an abnormally high sympathetic activity.

20. The method of claim 10, further comprising increasing said parasympathetic activity.

21. The method of claim 1, wherein said at least one beta-blocker is chosen from atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, pindolol, propranolol, sotalol, timolol, acebutalol, oxprenolol, carvedilol, and entbutolol.

22. The method of claim 1, wherein said method comprises increasing the parasympathetic activity/sympathetic activity ratio in at least a portion of said subject'"'"'s autonomic nervous system.

23. The method of claim 1, further comprising administering an effective amount of at least one non-beta-blocker agent.

24. The method of claim 23, wherein said at least one non-beta-blocker agent is chosen from aldosterone antagonists;

angiotensin II receptor blockades;

angiotensin converting enzyme inhibitors;

statins;

triglycerides lowering drugs;

niacin;

anti-diabetes agents;

immunomodulators;

nicotine;

sympathomimetics;

cholinergics;

acetylcholinesterase inhibitors;

magnesium and magnesium sulfates, calcium channel blockers;

muscarinics;

sodium channel blockers;

glucocorticoid receptor blockers;

peripheral andrenergic inhibitors;

blood vessel dilators;

central agonists;

combined alpha and beta-blockers;

alpha blockers;

combination diuretics;

potassium sparing diuretics;

nitrates;

cyclic nucleotide monophosphodiesterase inhibitors;

alcohols;

catecholamines inhibitors;

analgesics;

neurotoxins;

vasopressin inhibitors;

oxytocin inhibitors;

alcohol;

relaxin hormone;

renin inhibitors;

estrogen;

estrogen analogues;

estrogen metabolites;

progesterone inhibitors;

testosterone inhibitors;

gonadotropin-releasing hormone analogues;

gonadotropin-releasing hormone inhibitors;

vesicular monoamine transport inhibitors;

dipeptidyl peptidase IV inhibitors;

antihistamines and melatonin.

25. The method of claim 23, wherein said at least one beta-blocker and at least one non-beta-blocker are concomitantly administered in unit dosage form.

26. The method of claim 1, further comprising stimulating at least a portion of said subject'"'"'s autonomic nervous system.

27. The method of claim 26, wherein said stimulating comprises contacting at least a portion of said subject'"'"'s autonomic nervous system with at least one electrode and applying electrical energy to at least a portion of said subject'"'"'s autonomic nervous system.

28. The method of claim 1 wherein said at least one beta-blocker is administered orally at least once a day to said subject.

29. The method of claim 1, wherein said condition is a neurodegenerative condition chosen from the group of:

Alzheimer'"'"'s disease, Pick'"'"'s disease, dementia, delirium and amyotrophic lateral sclerosis.

30. The method of claim 1, wherein said condition is a neuroinflammatory condition chosen from the group of:

viral meningitis, viral encephalitis, fungal meningitis, fungal encephalitis, multiple sclerosis, charcot joint and myasthenia gravis.

31. The method of claim 1, wherein said condition is an orthopedic inflammatory condition chosen from the group of:

osteoarthritis, inflammatory arthritis, regional idiopathic osteoporosis, reflex sympathetic dystrophy, Paget'"'"'s disease and osteoporosis.

32. The method of claim 1, wherein said condition is a lymphoproliferative condition chosen from the group of:

lymphoma, lymphoproliferative disease, Hodgkin'"'"'s disease and inflammatory pseudomotor of the liver.

33. The method of claim 1, wherein said condition is an autoimmune condition chosen from the group of:

Graves disease, hashimoto'"'"'s, takayasu'"'"'s disease, kawasaki'"'"'s diseases, arteritis, scleroderma, CREST syndrome, allergies, dermatitis, Henoch-schlonlein purpura, goodpasture syndrome, autoimmune thyroiditis, myasthenia gravis, Reiter'"'"'s disease, raynaud'"'"'s, and lupus.

34. The method of claim 1, wherein said condition is an inflammatory condition chosen from the group of:

acute respiratory distress syndrome, multiple sclerosis, juvenile rheumatoid arthritis, juvenile chronic arthritis and rheumatoid arthritis.

35. The method of claim 1, wherein said condition is an infectious disease chosen from the group:

sepsis, viral and fungal infections, diseases of wound healing, wound healing, tuberculosis, infection, acquired immune deficiency syndrome and human immunodeficiency virus.

36. The method of claim 1, wherein said condition is a pulmonary condition chosen from the group of:

tachypnea, fibrotic lung diseases such as cystic fibrosis and the like, interstitial lung disease, desquamative interstitial pneumonitis, non-specific interstitial pneumonitis, lymphocytic interstitial pneumonitis, usual interstitial pneumonitis, idiopathic pulmonary fibrosis, pulmonary edema, aspiration, asphyxiation, pneumothorax, right-to-left shunts, left-to-right shunts and respiratory failure.

37. The method of claim 1, wherein said condition is a transplant-related condition chosen from the group of:

transplant rejection, transplant-related tachycardia, transplant related renal failure, transplant related bowel dysmotility and transplant-related hyperreninemia.

38. The method of claim 1, wherein said condition is a gastrointestinal condition chosen from the group of:

hepatitis, xerostomia, bowel mobility, peptic ulcer disease, constipation, ileus, irritable bowel syndrome, post-operative bowel dysmotility, inflammatory bowel disease and typhilitis.

39. The method of claim 1, wherein said condition is an endocrine condition chosen from the group of:

hypothyroidism, hyperglycemia, diabetes, obesity, syndrome X, insulin resistance and polycycstic ovarian syndrome.

40. The method of claim 1, wherein said condition is a skin condition chosen from the group of:

wrinkles, cutaneous vasculitis and psoriasis.

41. The method of claim 1, wherein said condition is an aging associated condition chosen from the group of:

shy dragers, multi-system atrophy, age related inflammation conditions, and cancer.

42. The method of claim 1, wherein said condition is a neurologic condition chosen from the group of:

epilepsy, seizures, stroke, insomnia, cerebral vascular accident, transient ischemic attacks, stress, bipolar disorder, concussions, post-concussive syndrome, cerebral vascular vasospasm, depression, schizophrenia, central sleep apnea and obstructive sleep apnea.

43. The method of claim 1, wherein said condition is aTh-2 dominant condition chosen from the group of:

typhilitis, osteoporosis, lymphoma, myasthenia gravis and lupus.

44. The method of claim 1, wherein said condition is a condition that causes at least one of:

hypoxia, hypercarbia, hypercapnia, acidosis and acidemia.

45. The method of claim 44, wherein said conditions is chosen from the group of:

acute pulmonary embolism, sudden infant death syndrome, sudden adult death syndrome, chronic pulmonary embolism, pleural effusion, cardiogenic pulmonary edema, non-cardiogenic pulmonary edema, acute respiratory distress syndrome, neurogenic edema, hypercapnia, academia, renal tubular acidosis and lung diseases that cause acidosis.

46. The method of claim 1, wherein said condition is a pediatric-related condition chosen from the group of:

respiratory distress syndrome, sudden infant death syndrome, hirschsprung disease, bronchopulmonary dysplasia, congenital megacolon and aganglionosis.

47. The method of claim 1, wherein said condition is an OB-GYN condition chosen from the group of:

amniotic fluid embolism, pregnancy-related arrhythmias, fetal stress syndrome, fetal hypoxia, menopausal mood disorders, premenstrual mood disorders, and amniotic fluid embolism.

48. The method of claim 1, wherein said condition is a sudden death syndrome chosen from the group of:

sudden infant death syndrome and sudden adult death syndrome.

49. The method of claim 1, wherein said condition is fibrosis.

50. The method of claim 1, wherein said condition is a post-operative recovery condition chosen from the group of:

post-operative pain, post operative ileus, post-operative fever and post-operative nausea.

51. The method of claim 1, wherein said condition is a post-procedural recovery condition chosen from the group of:

post-procedural pain, post procedural ileus, post-procedural fever and post-procedural nausea.

52. The method of claim 1, wherein said condition is chronic pain.

53. The method of claim 1, wherein said condition is trauma.

54. The method of claim 1, wherein said condition is a disorder of thermoregulation.

55. The method of claim 1, wherein said condition is cyclic vomiting syndrome.

56. An algorithm for administering said at least one beta-blocker to said subject in accordance with method of claim 1 recorded on a computer-readable medium.

57. A system comprising:

(a) an algorithm for administering said at least one beta-blocker to said subject in accordance with method of claim 1 recorded on a computer-readable medium

(b) a pharmaceutically effective amount of at least one beta-blocker, and

(c) a drug delivery device.

58. The system of claim 57, wherein said at least one beta-blocker is chosen from atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, pindolol, propranolol, sotalol, timolol, acebutalol, oxprenolol, carvedilol, and entbutolol.

59. The system of claim 57, wherein said drug delivery device is an implantable drug delivery device.

60. The system of claim 57, further comprising a pharmaceutically acceptable amount of at least one non-beta-blocker agent.

61. A kit comprising:

(a) a pharmaceutically effective amount of at least one beta-blocker; and

(b) instructions for practicing the method of claim 1.