Abstract
The blocking effect of three 5-HT(4) agonists, cisapride, mosapride, and the newly discovered CJ-033466 on the human ether-a-go-go-related gene (hERG) channel was studied using a whole cell patch-clamp technique in HEK293 cells. Cisapride was found to be the most potent of the hERG blockers. CJ-033466 had the widest safety margin between its hERG blocking activity and 5-HT(4) agonism among the tested compounds. This suggests a lower clinical risk of cardiac arrhythmia in CJ-033466 compared with the other 2 agonists. Therefore, CJ-033466 has the potential to be a drug with higher therapeutic efficacy and less cardiac risk than both cisapride and mosapride.
MeSH terms
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Aminopyridines / administration & dosage
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Aminopyridines / adverse effects
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Aminopyridines / pharmacology*
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Arrhythmias, Cardiac / chemically induced
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Benzamides / administration & dosage
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Benzamides / adverse effects
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Benzamides / pharmacology*
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Cell Line
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Cisapride / administration & dosage
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Cisapride / adverse effects
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Cisapride / pharmacology*
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Electrophysiology
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Ether-A-Go-Go Potassium Channels / drug effects*
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Imidazoles / administration & dosage
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Imidazoles / adverse effects
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Imidazoles / pharmacology*
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Inhibitory Concentration 50
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Morpholines / administration & dosage
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Morpholines / adverse effects
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Morpholines / pharmacology*
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Patch-Clamp Techniques
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Serotonin 5-HT4 Receptor Agonists
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Serotonin Receptor Agonists / administration & dosage
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Serotonin Receptor Agonists / adverse effects
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Serotonin Receptor Agonists / pharmacology*
Substances
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Aminopyridines
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Benzamides
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CJ 033466
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Ether-A-Go-Go Potassium Channels
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Imidazoles
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Morpholines
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Serotonin 5-HT4 Receptor Agonists
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Serotonin Receptor Agonists
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mosapride
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Cisapride