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Calcium Uptake Inhibition Activity

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Book cover Drug Discovery and Evaluation: Pharmacological Assays

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Abstract

Cellular calcium flux is regulated by receptor-operated and voltage-dependent channels, which are sensitive to inhibition by calcium entry blockers. The term calcium antagonist was introduced by Fleckenstein (1964, 1967) when two drugs, prenylamine and verapamil, originally found as coronary dilators in the Langendorff experiment, were shown to mimic the cardiac effects of simple Ca2+ withdrawal, diminishing Ca2+-dependent high-energy phosphate utilization, contractile force, and oxygen requirement of the beating heart without impairing the Na+-dependent action potential parameters. These effects were clearly distinguishable from β-receptor blockade and could promptly be neutralized by elevated Ca2+, β-adrenergic catecholamines, or cardiac glycosides, measures that restore the Ca2+ supply to the contractile system. In the following years, many Ca2+ antagonists were introduced to therapy. Specific Ca2+ antagonists interfere with the uptake of Ca2+ into the myocardium and prevent myocardial necrotization arising from deleterious intracellular Ca2+ overload. They act basically as specific inhibitors of the slow transsarcolemnal Ca2+ influx but do not or only slightly affect the fast Na+ current that initiates normal myocardial excitation.

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  1. CorDynamics, Inc., 2242 W. Harrison St., Suite 108, Chicago, IL, 60612, USA

    Michael Gralinski, Liomar A. A. Neves & Olga Tiniakova

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  1. Michael Gralinski
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  2. Liomar A. A. Neves
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  3. Olga Tiniakova
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Correspondence to Michael Gralinski .

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  1. CorDynamics, Dieburg, Germany

    Franz J. Hock

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Gralinski, M., Neves, L.A.A., Tiniakova, O. (2016). Calcium Uptake Inhibition Activity. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Cham. https://doi.org/10.1007/978-3-319-05392-9_6

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