Abstract
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:
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1.
Are there specific 1,4-dihydropyridine sites?
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2.
How many classes of such sites exist?
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3.
What are the structural demands at these sites?
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4.
How may activator and antagonist ligands be differentiated?
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a)
Structure
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b)
Mechanism
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a)
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5.
What is the relationship of binding sites to the Ca2+ channel and channel permeation processes?
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6.
What relationship does this site(s) have to the actions of other structural categories of Ca2+ channel ligands?
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7.
What is the basis for any tissue selectivity of the 1,4-dihydropyridines?
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8.
Are there endogenous ligands for the Ca2+ channel?
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References
Bean B (1984) Nitrendipine block of cardiac calcium channels: high affinity binding to the inactivated state. Proc Nat Acad Sci USA.
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.
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.
Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behaviour favored by dihydropyridine Ca agonists and antagonists. Nature.
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.
Janis RA, Triggle DJ (1983) New development in Ca2+ channel antagonists. J Med Chem 26:775–785.
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.
Langs DA, Triggle DJ (1984) Chemical structure and pharmacologic activities of Ca2+ channel antagonists. In: Proc 9th International Congress of Pharmacology, London, 1984.
Loev B, Goodman KM, Snader KM, Tedeschi R, Macko E (1974) “Hantzsch-type” dihydropyridine hypotensive agents. J Med Chem 17:956–965.
Mannhold R, Rodenkirchen R, Bayer R (1982) Qualitative and quantitative structure-activity relationships of specific Ca antagonists. Prog Pharmacol 5:25–52.
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.
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.
Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303:535–538.
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.
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.
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.
Triggle AM, Shefter E, Triggle DJ (1980) Crystal structures of calcium channel antagonists. J Med Chem 23:1442–1445.
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Su, C.M., Yousif, F.B., Triggle, D.J., Janis, R.A. (1985). Structure-Function Relationships of 1,4-Dihydropyridines: Ligand and Receptor Perspectives. In: Fleckenstein, A., Van Breemen, C., Gross, R., Hoffmeister, F. (eds) Cardiovascular Effects of Dihydropyridine-Type Calcium Antagonists and Agonists. Bayer-Symposium, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70499-4_7
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