Biomedical Engineering Reference
In-Depth Information
Calcium Ion Channels and Their Blockers
Dimitra Hadjipavlou-Litina
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
1.1 Calcium Ion Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 266
2 Calcium Ion Channel Blockers . . . .......................................................... 267
2.1 Mechanism of Action ................................................................. 267
2.2 Classification of Calcium Ion Channel Blockers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268
3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 282
Abstract Calcium is a ubiquitous second messenger. Calcium entry into the
cytosol is mediated by multiple types of calcium channels each with a distinct
physiological role. There exist five different types of voltage-dependent Ca
2
þ
channel. The calcium ion channel blocking agents are a chemically, pharmaco-
logically, and therapeutically heterogeneous group of drugs. Most calcium channel
blockers decrease the force of contraction of the myocardium resulting in a
decrease in blood pressure. Representative classes include: (a) dihydropyridines
and (b) nondihydropyridines. Structure-activity relationship studies and the struc-
tural features that are characterized as prerequisite for the calcium ion channel-
blocking activity indicate that the presence of a C-4 phenyl group is a preferential
requirement to optimize the biological activity. Steric hindrance is shown to be
significant. No relationship of activity is indicated with electronic or lipophilic
properties.
Keywords Calcium ion channels • Calcium channel blockers • Therapeutic
potential • Structure-activity relationships
