Claims
- 1. A method of treating cardiac arrhythmia in mammals, comprising block of the slowly activating delayed rectifier potassium (K+) current (I.sub.Ks) and the rapidly activating and deactivating delayed rectifier potassium current (I.sub.Kr) through the administration of a 1,4-benzodiazepine compound or a benzodiazepine derivative, wherein the 1,4-benzodiazepine or benzodiazepine derivative provides 50% block of the slowly activating delayed rectifier potassium (K+) current (IKs) in isolated myocytes at a concentration of 1 uM or less and wherein the 1,4-benzodiazepine exhibit a selectivity ratio of greater than 10 over blockade of IKr, IK1 and ICa.
- 2. The method of claim 1 wherein the benzodiazepine or benzodiazepine derivative is selected from the group consisting of 3(R)-(+)-1,3-dihydro-3-(2-indolecarbonylamino)-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one; (S)-(-)-1,3-dihydro-3-(2-indolecarbonylamino)-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one; N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N'-(3-methylphenyl)urea; (R)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N'-(3-methylphenyl)urea; N-[3(R,S)-5-cyclohexyl-2,3-dihydro-1-methyl-2-oxo-1H-1,4-benzodiazepin-3-yl]-N'-[3-(isopropyl sulfonylaminocarbonyl)phenyl]urea; N,N-dimethyl-4-(3(R,S)-(((3-methylphenyl)amino)-carbonyl)amino-1,3-dihydro-1-(2-methylpropyl)-2-oxo-1,4-benzodiazepin-5-yl)phenylmethylamine; (R)-3-amino-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one; N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-N'-(m-methylphenyl)urea; (..+-..)-N-(2,3-dihydro-1-methyl-2-oxo-5-(4-pyridinyl)-1H-1,4-benzodiazepin-3-yl-1H-indole-2-carboxamide; N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl)-4-methylbenzenesulfonamide;.(R)-1-(2-(dimethyl aminoethyl)-5-(2-fluorophenyl)-1,3-dihydro-3-((1-methyl-1H-indole-3-yl)methyl)-2H-benzodiazepin-2-one; N-(2,3-dihydro-1-methyl-2-oxo-5-(4-morpholino)-1H-1,4-benzodiazepin-3-yl)-N'-3-methylphenylurea.
- 3. The method of claim 1 wherein the block prolongs the cardiac refractory period equally or to a greater extent as heart rate increases.
- 4. The method of claim 3 wherein the block is independent of heart rate.
CROSS REFERENCE
This is a continuation in part of U.S. patent application Ser. No. 08/018,912 which was filed on Feb. 17, 1993, now abandoned, which is a continuation of U.S. patent application Ser. No. 07/802,000 which was filed on Dec. 3, 1991, now abandoned.
US Referenced Citations (9)
Foreign Referenced Citations (6)
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Continuations (1)
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Date |
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Parent |
802000 |
Dec 1991 |
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Continuation in Parts (1)
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18912 |
Feb 1993 |
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