Adenosine antagonists in the treatment and diagnosis of A-V node conduction disturbances

• US 4,364,922 A
• Filed: 10/14/1980
• Issued: 12/21/1982
• Est. Priority Date: 10/14/1980
• Status: Expired due to Term

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: The University of Virginia Patent Foundation
• Inventors: Belardinelli, Luiz, Rubio, Rafael, Berne, Robert M.
• Primary Examiner(s): Fagelson, Anna P.
• Application Number:
  US06/196,652
• Time in Patent Office: 798 Days
• Field of Search: 424/9, 424/253, 424/265
• US Class Current: 424/9.1
• 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 31/46 8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine

Abstract

A method of relieving atrioventricular conduction block by administering to a human or animal an effective amount of an adenosine antagonist that competitively inhibits adenosine or that reduces the level of adenosine present in myocardial tissue and associated fluids. A method of diagnosing atrioventricular conduction block caused by ischemia of the heart by measuring the time delay between atrial and ventricular excitation before and after the administration of an adenosine antagonist. Specific antagonists disclosed include methylxanthines.

Claims

1. A method of treating atrioventricular conduction block, comprising the steps of:

administering to a human or animal with an atrioventricular conduction block an amount of an antagonist of adenosine sufficient to alleviate atrioventricular conduction block, wherein said antagonist competitively inhibits adenosine or reduces the level of adenosine present in myocardial tissue and associated fluids.

2. A method of treating atrioventricular conduction block according to claim 1, wherein said antagonist is a methylxanthine.

3. A method of treating atrioventricular conduction block according to claim 2, wherein said methylxanthine is administered in a dosage of 0.1-20 mg/kg.

4. A method of treating atrioventricular conduction block according to claim 2, wherein said methylxanthine is administered in a dosage of 0.45-10 mg/kg.

5. A method of treating atrioventricular conduction block according to claim 2, wherein said methylxanthine is administered in a dosage of 3-5 mg/kg.

6. A method of treating atrioventricular conduction block according to claims 2, 3, 4, or 5, wherein said methyl xanthine is theophylline or a derivative thereof.

7. A method of treating atrioventricular conduction block according to claim 6, wherein said administration is by intravenous injection.

8. A method of treating atrioventricular conduction block according to claim 6, wherein said administration is by oral ingestion.

9. A method of treating atrioventricular conduction block according to claim 6, wherein said administration is by insertion of a suppository.

10. A method of treating atrioventricular conduction block according to claim 6, wherein said theophylline derivative is aminophylline.

11. A method of treating atrioventricular conduction block according to claim 10, wherein said administration is by intraveneous injection.

12. A method of treating atrioventricular conduction block according to claim 10, wherein said administration is by oral ingestion.

13. A method of treating atrioventricular conduction block according to claim 10, wherein said administration is by insertion of a suppository.

14. A method of treating atrioventricular conduction block according to claim 2, wherein said administration is a continuous intraveneous injection.

15. A method of treating atrioventricular conduction block according to claim 14, wherein said continuous intravenous injection is at a rate of about 0.45 mg/kg/hr.

16. A method of treating atrioventricular conduction intravenous according to claims 14 o4 15, wherein said methylxanthine is theophylline or a derivative thereof.

17. A method of treating atrioventricular conduction block according to claim 16, wherein said theophylline derivative is aminophylline.

18. A method of treating atrioventricular conduction block according to claim 1, wherein said administration occurs concurrently with administration of atropine.

19. A method of treating atrioventricular conduction block according to claim 6, wherein said administration occurs concurrently with administration of atropine.

20. A method of treating atrioventricular conduction block according to claim 10, wherein said administration occurs concurrently with administration of atropine.

21. A method of treating atrioventricular conduction block according to claim 20, wherein 0.1-3 mg of said atropine is administered.

22. A method of diagnosing atrioventricular conduction block, comprising the steps of:

administering an antagonist of adenosine to a human or other animal, wherein said antagonist competitively inhibits adenosine or reduces the levels of adenosine present in myocardial tissue and associated fluids; and

monitoring the delay between atrial and ventricular contraction.

23. A method of diagnosing atrioventricular conduction block according to claim 22, wherein said monitoring is by electrocardiography.

24. A method of diagnosing atrioventricular conduction block according to claim 23, wherein said antagonist is a methylxanthine.

25. A method of diagnosing atrioventricular conduction block according to claim 24, wherein said methylxanthine is theophylline or a derivative thereof.

26. A method of diagnosing atrioventricular conduction block according to claim 25, wherein said theophylline derivative is aminophylline.

27. A method of diagnosing atrioventricular conduction block according to claims 23, 24, 25 or 26, wherein said administration is by intravenous injection.