Ion channel modulating compounds and uses thereof
Ion channel modulating compounds are disclosed. The compounds of the present invention may be incorporated in compositions and kits. The present invention also discloses a variety of in vitro and in vivo uses for the compounds and compositions, including the treatment of arrhythmia and the production of analgesia and local anesthesia.
1. A method of treating arrhythmia in a warm-blooded animal, comprising administering to said animal a therapeutically effective amount of a composition comprising a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, excipient or diluent.
2. The method of claim 1 wherein administration is by a route selected from the group consisting of oral, topical, parenteral, sublingual, rectal, vaginal, and intranasal.
3. The method of claim 2 wherein the parenteral administration is selected from the group consisting of subcutaneous injection, intravenous injection, intramuscular injection, epidural injection, intrastemal injection, and infusion.
4. The method of claim 2 wherein the oral administration comprises administering an oral dosage form selected from the group consisting of a powder, a granule, a compressed tablet, a pill, a capsule, a cachet, a chewing gum, a wafer, and a lozenge.
5. The method of claim 1 wherein the arrhythmia is atrial arrhythmia.
6. The method of claim 5 wherein the atrial arrhythmia is atrial fibrillation.
7. The method of claim 1 wherein the arrhythmia is ventricular arrhythmia.
8. The method of claim 7 wherein the ventricular arrhythmia is ventricular fibrillation.
9. The method of claim 8 wherein the ventricular fibrillation occurs during acute ischemia.
10. A method for blocking cardiac early repolarizing currents and cardiac sodium currents in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a composition comprising a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, excipient or diluent.
11. The method of claim 10 wherein the blocking occurs in the presence of an arrhythmogenic substrate in the heart.
12. A method to block sodium or potassium ion channels in vitro comprising contacting a preparation containing sodium ion channels or potassium ion channels with an effective amount of a composition comprising a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, excipient or diluent.
13. A method to block sodium or potassium ion channels in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a composition comprising a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, excipient or diluent.
14. A method for treating atrial arrhythmia in a warm-blooded animal, the method comprising administering to said animal a therapeutically effective amount of a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof.
15. A method to produce local analgesia or anesthesia in a warm-blooded animal comprising administering to said animal a therapeutically effective amount of a composition comprising a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier, excipient or diluent.
16. A method for treating atrial fibrillation in a warm-blooded animal, the method comprising administering to said animal a therapeutically effective amount of a compound having the following structure:
as an isolated enantiomeric or diastereomeric isomer or as a mixture thereof, or as a pharmaceutically acceptable salt thereof.
17. The method of any one of claims 1 - 6 and 7 - 16 wherein the compound is a mixture of isomers.
18. The method of claim 17 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
19. The method of claim 17 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
20. The method of any one of claims 1 - 6 and 7 - 16 wherein the compound is an isolated enantiomeric or diastereomeric isomer.
21. The method of claim 20 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
22. The method of claim 20 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
23. The method of claim 20 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
24. The method of claim 20 wherein the compound has the following structure:
or pharmaceutically acceptable salt thereof.
25. The method of claim 22 wherein the pharmaceutically acceptable salt is a monohydrochloride salt.