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(-)[3H]amlodipine binding to rat cardiac membranes
1Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Vic, Australia.
Journal of Cardiovascular Pharmacology
|April 1, 1991
Summary
Amlodipine, a calcium channel blocker, binds to multiple sites in heart membranes, including those for phenylalkylamine antagonists. This binding is stereospecific and affected by pH and temperature.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Biochemistry
Background:
- Amlodipine is a novel, long-acting dihydropyridine calcium antagonist.
- Understanding its precise binding characteristics is crucial for its therapeutic application.
Purpose of the Study:
- To comprehensively characterize the binding properties of amlodipine.
- To investigate its affinity and specificity for cardiac calcium channels.
Main Methods:
- Saturation binding studies were performed using radiolabeled (-)[3H]amlodipine.
- Rat cardiac membrane fragments were utilized as the binding substrate.
- Inhibition studies were conducted with various calcium channel blockers.
Main Results:
- (-)[3H]Amlodipine demonstrated high-affinity binding to a single site (KD = 1.68 nM).
- Binding was stereoselective, pH- and temperature-sensitive, and reached equilibrium within 5 hours.
- Amlodipine exhibited strong binding to phenylalkylamine recognition sites, in addition to dihydropyridine and benzothiazepine sites.
- Inhibition by D600 was stereospecific, with the (-) enantiomer being more potent.
Conclusions:
- Amlodipine binds to multiple calcium channel subtypes in cardiac membranes.
- Its binding profile suggests a broader interaction than initially anticipated for dihydropyridines.
- These findings provide insights into the molecular pharmacology of amlodipine and its interaction with cardiac calcium channels.