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Chemical Compound Review

DynaCirc     propan-2-yl methyl 2,6-dimethyl-4-(8-oxa-7...

Synonyms: isradipine, Lomir, PN-200-110, PN-205-033, PN-205-034, ...
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Disease relevance of DynaCirc


Psychiatry related information on DynaCirc


High impact information on DynaCirc

  • OBJECTIVE: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide [10].
  • This heterogeneity in response of presynaptic boutons was not seen with isradipine (5 microM) or omega-agatoxin IVA (80 nM), which inhibited exocytosis by 23% and 17%, respectively [11].
  • Only one type, the family of L-type Ca2+ channels (L channels), contains high-affinity binding domains within their alpha 1-subunits for different chemical classes of drugs (Ca2+ channel antagonists; exemplified by isradipine, verapamil and diltiazem) [12].
  • Treatment of postoperative hypertension after coronary artery bypass surgery. Double-blind comparison of intravenous isradipine and sodium nitroprusside [1].
  • Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall [13].

Chemical compound and disease context of DynaCirc


Biological context of DynaCirc


Anatomical context of DynaCirc

  • The thrombin-induced contraction of portal vein strips was completely inhibited by isradipine, and thrombin did not produce an increase in cytosolic [Ca2+], measured by indo-1 fluorescence in cells clamped at -50 mV, sufficient to activate Ca(2+)-dependent chloride current.(ABSTRACT TRUNCATED AT 250 WORDS)[22]
  • The observed inhibition by PN 200-110 may relate to mitogen responses of the smooth muscle cell in the vessel wall (migration and proliferation) involved in lesion progression after endothelial damage [20].
  • No data are available on the effects of isradipine on a compromised sinus node [23].
  • Earlier studies have shown isradipine to reduce the size of infarct in a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery) (Sauter A, Rudin M: Stroke 1986; 17: 1228-1234) [24].
  • It is concluded that isradipine in hemodynamically effective doses has no depressant effect on sinus and atrioventricular node function in patients with sick sinus syndrome [23].

Associations of DynaCirc with other chemical compounds


Gene context of DynaCirc

  • Here we demonstrate that the four Ca(2+)-channel blockers, Amlodipine, Felodipine, Isradipine and Manidipine, at nanomolar concentrations, activate the transcription of the genes encoding IL-6 and IL-8 in primary human VSMC and fibroblasts [29].
  • 2. The results showed that BQ123 and the calcium antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed IMA precontracted with 3 nmol/L ET-1 with the EC50 values of 7.18 +/- 0.09 (-log mol/L) for BQ123, and 7.68 +/- 0.07, 7.02 +/- 0.12, 6.96 +/- 0.08 and 6.89 +/- 0.09 for the calcium antagonists, respectively [30].
  • In bFGF-stimulated SMCs, amlodipine and isradipine reduced both Ca2+ influx and ERK 1/2 activation without affecting Ca2+ mobilization [31].
  • Reducing BP with isradipine or atenolol results in a similar decrease in platelet activity and PAI-level, tested at rest and 1 h after rest, respectively [32].
  • Se-EPO was not changed by the calcium antagonist, isradipine [33].

Analytical, diagnostic and therapeutic context of DynaCirc

  • Isradipine reversed AA constriction induced by both peptides [18].
  • Furthermore, PN 200-110 did not reduce the extent of platelet deposition (compared with controls) occurring at the denuded vessel surface 1 hour or 24 hours after balloon catheterization, which indicates that the inhibition of lesion development may not reflect an antiplatelet mechanism [20].
  • Twenty-three men with essential hypertension participated in a double-blind placebo-controlled study with a crossover design to evaluate the long-term (nine weeks) effects of isradipine on central and renal hemodynamics [34].
  • Because of the preference of isradipine for the arterial side of the peripheral vascular tree, the mean peripheral perfusion pressure remained higher in this group than in the atenolol group, although central systemic blood pressure was lowered equally and satisfactorily in both groups [27].
  • It is concluded that a slow titration of isradipine by increments at three-week intervals results in an effective and well-tolerated treatment for essential hypertension, both in mono- and combination therapy [35].


  1. Treatment of postoperative hypertension after coronary artery bypass surgery. Double-blind comparison of intravenous isradipine and sodium nitroprusside. Leslie, J., Brister, N., Levy, J.H., Yared, J.P., Marty, A., Martin, H., Hines, R., Savino, J., Cohen, M. Circulation (1994) [Pubmed]
  2. Safety and efficacy of isradipine, alone and in combination, in the treatment of angina pectoris. Rüegg, P.C., Nelson, D.J. Am. J. Med. (1989) [Pubmed]
  3. Use of isradipine in hypertension following coronary artery bypass surgery. Underwood, S.M., Feneck, R.O., Davies, S.W., Walesby, R.K., Lunnon, M.W. Am. J. Med. (1989) [Pubmed]
  4. Hemodynamic study of short- and long-term isradipine treatment in patients with chronic ischemic congestive heart failure. McGrath, B.P., Newman, R., Older, P. Am. J. Med. (1989) [Pubmed]
  5. Isradipine suppresses amphetamine-induced conditioned place preference and locomotor stimulation in the rat. Pucilowski, O., Płaźnik, A., Overstreet, D.H. Neuropsychopharmacology (1995) [Pubmed]
  6. Phenytoin/isradipine interaction causing severe neurologic toxicity. Cachat, F., Tufro, A. The Annals of pharmacotherapy. (2002) [Pubmed]
  7. Does isradipine modified release 5 mg once daily reduce blood pressure for 24 hours? Celis, H., Staessen, J., Fagard, R., Thijs, L., Amery, A. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  8. Bioavailability of isradipine in young and old rats: effect of mode of administration. Tse, F.L., Jaffe, J.M., Hassell, A.E., Schran, H.F. J. Pharm. Pharmacol. (1989) [Pubmed]
  9. The effect of isradipine on maximal electroshock seizures in mice. Ozyazgan, S., Senses, V., Utkan, T., Yildiran, G., Ulak, G., Gacar, N., Ozüner, Z., Akkan, A.G. Gen. Pharmacol. (1998) [Pubmed]
  10. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. Borhani, N.O., Mercuri, M., Borhani, P.A., Buckalew, V.M., Canossa-Terris, M., Carr, A.A., Kappagoda, T., Rocco, M.V., Schnaper, H.W., Sowers, J.R., Bond, M.G. JAMA (1996) [Pubmed]
  11. Measurements of exocytosis from single presynaptic nerve terminals reveal heterogeneous inhibition by Ca(2+)-channel blockers. Reuter, H. Neuron (1995) [Pubmed]
  12. Structural basis of drug binding to L Ca2+ channels. Striessnig, J., Grabner, M., Mitterdorfer, J., Hering, S., Sinnegger, M.J., Glossmann, H. Trends Pharmacol. Sci. (1998) [Pubmed]
  13. Effect of chronic dihydropyridine (isradipine) on the large arterial walls of spontaneously hypertensive rats. Levy, B.I., Duriez, M., Phillipe, M., Poitevin, P., Michel, J.B. Circulation (1994) [Pubmed]
  14. Cardiovascular and renal effects of single administration of three different doses of isradipine in hypertensive patients. Dose-response curves of the different effects. Rupoli, L., Fruscio, M., Gradnik, R., Chianca, R., Leonetti, G., Zanchetti, A. Am. J. Med. (1989) [Pubmed]
  15. Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group. Papademetriou, V., Gottdiener, J.S., Narayan, P., Cushman, W.G., Zachariah, P.K., Gottdiener, P.S., Chase, G.A. J. Am. Coll. Cardiol. (1997) [Pubmed]
  16. Additive effect of isradipine in combination with captopril in hypertensive patients. Eggertsen, R., Svensson, A., Dahlöf, B., Hansson, L. Am. J. Med. (1989) [Pubmed]
  17. Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy. Guasch, A., Parham, M., Zayas, C.F., Campbell, O., Nzerue, C., Macon, E. J. Am. Soc. Nephrol. (1997) [Pubmed]
  18. Protein kinase C and calcium channel activation as determinants of renal vasoconstriction by angiotensin II and endothelin. Takenaka, T., Forster, H., Epstein, M. Circ. Res. (1993) [Pubmed]
  19. Synergistic actions of glucagon and miniglucagon on Ca2+ mobilization in cardiac cells. Sauvadet, A., Rohn, T., Pecker, F., Pavoine, C. Circ. Res. (1996) [Pubmed]
  20. Suppression of rat carotid lesion development by the calcium channel blocker PN 200-110. Handley, D.A., Van Valen, R.G., Melden, M.K., Saunders, R.N. Am. J. Pathol. (1986) [Pubmed]
  21. Cytosolic Ca2+ of excitable pituitary cells at resting potentials is controlled by steady state Ca2+ currents sensitive to dihydropyridines. Mollard, P., Theler, J.M., Guérineau, N., Vacher, P., Chiavaroli, C., Schlegel, W. J. Biol. Chem. (1994) [Pubmed]
  22. Dual effect of thrombin on voltage-dependent Ca2+ channels of portal vein smooth muscle cells. Baron, A., Loirand, G., Pacaud, P., Mironneau, C., Mironneau, J. Circ. Res. (1993) [Pubmed]
  23. Cardiac electrophysiologic properties of intravenous isradipine in patients with sick sinus syndrome. van Wijk, L.M., van Gelder, I., Crijns, H.J., van den Toren, E.W., Lie, K.I., Rüegg, P.C. Am. J. Med. (1989) [Pubmed]
  24. Treatment of hypertension with isradipine reduces infarct size following stroke in laboratory animals. Sauter, A., Rudin, M. Am. J. Med. (1989) [Pubmed]
  25. Analysis of the properties of binding of calcium-channel activators and inhibitors to dihydropyridine receptors in chick heart membranes. Maan, A.C., Hosey, M.M. Circ. Res. (1987) [Pubmed]
  26. Palmitate stimulation of glucagon secretion in mouse pancreatic alpha-cells results from activation of L-type calcium channels and elevation of cytoplasmic calcium. Olofsson, C.S., Salehi, A., Göpel, S.O., Holm, C., Rorsman, P. Diabetes (2004) [Pubmed]
  27. Differential effects of isradipine and atenolol on peripheral hemodynamics and arterial compliance. Jespersen, L.T., Krusell, L.R., Sihm, I., Pedersen, O.L. Am. J. Med. (1989) [Pubmed]
  28. Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives. A multicenter evaluation. Prisant, L.M., Carr, A.A., Nelson, E.B., Winer, N., Velasquez, M.T., Gonasun, L.M. Arch. Intern. Med. (1989) [Pubmed]
  29. Ca(2+)-channel blockers modulate the expression of interleukin-6 and interleukin-8 genes in human vascular smooth muscle cells. Rödler, S., Roth, M., Nauck, M., Tamm, M., Block, L.H. J. Mol. Cell. Cardiol. (1995) [Pubmed]
  30. Effects of calcium- and ETA-receptor antagonists on endothelin-induced vasoconstriction and levels of endothelin in the human internal mammary artery. Liu, J.J., Casley, D., Wojta, J., Gallicchio, M., Dauer, R., Johnston, C.I., Buxton, B.F. Clin. Exp. Pharmacol. Physiol. (1994) [Pubmed]
  31. Dual mechanism of action of amlodipine in human vascular smooth muscle cells. Stepien, O., Zhang, Y., Zhu, D., Marche, P. J. Hypertens. (2002) [Pubmed]
  32. Does calcium channel blockade and beta-adrenergic blockade affect platelet function and fibrinolysis to a varying degree? Gleerup, G., Mehlsen, J., Winther, K. J. Cardiovasc. Pharmacol. (1995) [Pubmed]
  33. Erythropoietin in chronic obstructive pulmonary disease. Relationship between serum erythropoietin, blood hemoglobin and lung function--effect of the calcium antagonist isradipine on serum erythropoietin. Graudal, N., Galløe, A.M., Nielsen, O.J. Respiration; international review of thoracic diseases. (1991) [Pubmed]
  34. Renal and hemodynamic effects of isradipine in essential hypertension. Persson, B., Andersson, O.K., Wysocki, M., Hedner, T., Aurell, M. Am. J. Med. (1989) [Pubmed]
  35. A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension. Sundstedt, C.D., Rüegg, P.C., Keller, A., Waite, R. Am. J. Med. (1989) [Pubmed]
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