Key result
In vitro 3H-Nimodipine binding studies demonstrate that calcium antagonist drugs can be divided into three main classes based on their interaction with the calcium channel binding site.
In vitro radioligand binding studies with 3H-Nimodipine demonstrate that voltage-operated calcium channels contain multiple regulatory sites, allowing the differentiation of calcium antagonist drugs into three distinct classes.
Answers are grounded in this paper and cite their sources.
No immediate clinical guidance for calcium antagonist selection; leaves open whether three binding classes enable targeted drug development.
3H-Nimodipine (3H-NIM) is a high affinity radioligand suitable to study Ca2+ -channels in a variety of tissues. The binding is saturable, reversible, and stereospecific in purified bovine heart and partially purified guinea-pig brain membranes. In the latter a Bmax of 600fmol/mg protein, dissociation constants (KD) of 0.4-0.8nM and a Hill slope of 1.0 are found. At 37 degrees C the optimal pH in 50mM TRIS-HCl buffer is 7.1-7.4. The calcium channel is a metalloprotein, and the divalent cation which is essential for the binding of 3H-NIM can be removed by EDTA (EC50 20 microM); the nimodipine binding site of the channel may then be reconstituted by divalent cations with Mn2+ greater than Ca2+ greater than Mg2+ greater than Sr2+. Ca2+ -antagonist drugs can be divided into three main classes based on their interaction with the 3H-NIM binding site: Class I has one site law of mass action-displacement isotherms with 3H-NIM, Class II exhibits complex biphasic inhibition profiles and Class III drugs increase the affinity of 1,4 dihydropyridines for the Ca2+ -channel. Diltiazem is a Class III Ca2+ -antagonist. Our in vitro studies lead us to conclude that the Ca2+ -channel contains multiple regulatory sites at which drugs can act.
No takes yet. Share an insight, caveat, or question.
Glossmann et al. (1983) studied this question. 3H-Nimodipine was evaluated on Binding characteristics to calcium channels. In vitro 3H-Nimodipine binding studies demonstrate that calcium antagonist drugs can be divided into three main classes based on their interaction with the calcium channel binding site.
Synapse has enriched 10 related papers. Consider them for comparative context: