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A molecular graphics study on structure-action relationships of calcium-antagonistic and agonistic 1,4-dihydropyridines

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Summary

Based on force field and quantum chemical calculations a hypothesis on the molecular mechanism of Ca channel-modulating 1,4-dihydropyridines (DHPs) has been developed. A careful investigation of the molecular electrostatic fields of the compounds led to the discovery of a unique area of the molecular potentials where Ca agonists and antagonists possess potentials with opposite sign. It is further demonstrated that the molecular potential of a simple receptor site model is reduced by interaction with Ca channel-activating DHPs and on the contrary increased by Ca channel-blocking DHPs. It is concluded that these effects could be the basis for opposite actions of 1,4-dihydropyridine enantiomers at the potential-dependent Ca channels.

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Author notes

  1. H. -D. Höltje

    Present address: Department of Pharmacy, Free University of Berlin, Königin-Luise-Strasse 2+4, D-1000, Berlin, F.R.G.

Authors and Affiliations

  1. Pharmaceutical Institute, University of Bern, Baltzerstrasse 5, CH-3012, Bern, Switzerland

    H. -D. Höltje & S. Marrer

Authors
  1. H. -D. Höltje
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  2. S. Marrer
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Höltje, H.D., Marrer, S. A molecular graphics study on structure-action relationships of calcium-antagonistic and agonistic 1,4-dihydropyridines. J Computer-Aided Mol Des 1, 23–30 (1987). https://doi.org/10.1007/BF01680555

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  • DOI: https://doi.org/10.1007/BF01680555

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