Structure-Function Relationships of 1,4-Dihydropyridines: Ligand and Receptor Perspectives

  • C. M. Su
  • F. B. Yousif
  • D. J. Triggle
  • R. A. Janis
Conference paper
Part of the Bayer-Symposium book series (BAYER-SYMP, volume 9)


The synthetic methodology previously outlined (Meyer, this volume) for the 1,4-dihydropyridines has made available numerous analogs with which to generate structure-activity data and attempt to solve a number of important questions concerning the actions of this class of drugs. Amongst the questions to be answered are the following:
  1. 1.

    Are there specific 1,4-dihydropyridine sites?

  2. 2.

    How many classes of such sites exist?

  3. 3.

    What are the structural demands at these sites?

  4. 4.
    How may activator and antagonist ligands be differentiated?
    1. a)


    2. b)


  5. 5.

    What is the relationship of binding sites to the Ca2+ channel and channel permeation processes?

  6. 6.

    What relationship does this site(s) have to the actions of other structural categories of Ca2+ channel ligands?

  7. 7.

    What is the basis for any tissue selectivity of the 1,4-dihydropyridines?

  8. 8.

    Are there endogenous ligands for the Ca2+ channel?



Calcium Channel Antagonist Tonic Component Radioligand Binding Study Calcium Antag Dihydropyridine Calcium Channel Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bean B (1984) Nitrendipine block of cardiac calcium channels: high affinity binding to the inactivated state. Proc Nat Acad Sci USA.Google Scholar
  2. Bolger GT, Gengo P, Klockowski R, Luchowski E, Siegel H, Janis RA, Triggle AM, Triggle DJ (1983) Characterization of binding of the Ca2+-channel antagonist [3H]nitrendipine, to guinea pig ileal smooth muscle. J Pharmacol Exptl Therap 225:291–310.Google Scholar
  3. Fossheim R, Svarteng K, Mostad A, Rømming C, Shefter E, Triggle DJ (1982) Crystal structures and pharmacological activity of calcium channel antagonists. J Med Chem 25:126–131.PubMedCrossRefGoogle Scholar
  4. Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behaviour favored by dihydropyridine Ca agonists and antagonists. Nature.Google Scholar
  5. Janis RA, Sarmiento JG, Maurer SC, Bolger GT, Triggle DJ (1984) Characteristics of the binding of [3H]nitrendipine to rabbit ventricular membranes: modification by other Ca++ channel antagonists and by the Ca2+ channel agonist BAY K 8644. J Pharmacol Exptl Therap 231:8–15.Google Scholar
  6. Janis RA, Triggle DJ (1983) New development in Ca2+ channel antagonists. J Med Chem 26:775–785.PubMedCrossRefGoogle Scholar
  7. Kokubun S, Reuter H (1984) Dihydropyridine derivatives prolong the open state of Ca2- channels in cultured cardiac cells. Proc Nat Acad Sci USA 81:4824–4827.PubMedCrossRefGoogle Scholar
  8. Langs DA, Triggle DJ (1984) Chemical structure and pharmacologic activities of Ca2+ channel antagonists. In: Proc 9th International Congress of Pharmacology, London, 1984.Google Scholar
  9. Loev B, Goodman KM, Snader KM, Tedeschi R, Macko E (1974) “Hantzsch-type” dihydropyridine hypotensive agents. J Med Chem 17:956–965.PubMedCrossRefGoogle Scholar
  10. Mannhold R, Rodenkirchen R, Bayer R (1982) Qualitative and quantitative structure-activity relationships of specific Ca antagonists. Prog Pharmacol 5:25–52.Google Scholar
  11. Rosenberger LB, Triggle DJ (1978) Calcium, calcium translocation and specific calcium antagonists. In: Weiss GB (ed) Calcium and drug action. Plenum Press, New York, pp 3–31.Google Scholar
  12. Sanguinetti MC, Kass RS (1984) Voltage-dependent block of calcium channel current in calf cardiac Purkinje fiber by dihydropyridine calcium channel antagonists. Circ Res 55:336–348.PubMedGoogle Scholar
  13. Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303:535–538.PubMedCrossRefGoogle Scholar
  14. Seidel W, Meyer H, Born L, Kazda S, Dompert W (1984) Rigid calcium antagonists of the nifedipine type: geometrical requirements for the dihydropyridine receptor. Abs 14 Div Med Chem American Chemical Society, 187th National Meeting, St. Louis, MO, April 8-13.Google Scholar
  15. Su CM, Swamy VC, Triggle DJ (1984) Calcium channel activation in vascular smooth muscle by BAY K 8644. Can J Physiol Pharmacol 62:1401–1410.PubMedCrossRefGoogle Scholar
  16. Yousif FB, Bolger GT, Ruzycky A, Triggle DJ (1985) Ca2+ channel antagonist actions in smooth muscle: Pharmacologic and radioligand binding studies. Can J Physiol Pharmacol 63:453–462.PubMedCrossRefGoogle Scholar
  17. Triggle AM, Shefter E, Triggle DJ (1980) Crystal structures of calcium channel antagonists. J Med Chem 23:1442–1445.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • C. M. Su
  • F. B. Yousif
  • D. J. Triggle
  • R. A. Janis

There are no affiliations available

Personalised recommendations