Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Contemporary scientific data about mode of action of calcium channel blocker — amlodipine, its pleiotropic effect (influence on endothelial function and antiatherogenic action) is presented. Amlodipine reduces proliferation of vascular smooth muscle cells and extracellular matrix, improves the vasodilating function of endothelial cells although they have no L-type calcium channels. It puts into action through stimulation of nitric oxide (NO) secretion in endothelium. Results of experimental studies on the role of S- and R-isomers of amlodipine in hemodynamic and pleiotropic effects are presented. S-isomer is pharmacologically active blocker of L-type calcium channel while the R-isomer is responsible for NO release. Drugs based on S-amlodipine have been developed. Bioequivalence of the S-amlodipine and amlodipine in doses of 5 and 10 mg, respectively , is shown. Mean values of systolic and diastolic blood pressure, heart rate were not different significantly according to pharmacodynamic studies of S-amlodipine 5 mg and amlodipine 10 mg. S-amlodipine demonstrated better tolerability and lower incidence of ankle edema than amlodipine. Further long-term studies on S-amlodipine effect on hard endpoints are needed.

About the Author

M. V. Leonova
Russian State Medical University
Russian Federation


1. Leonova M.V., Belousov Yu.B., Shteynberg L.L. et al. Analysis of pharmacotherapy of hypertension on the results of the study PIFAGOR III (survey of patients with hypertension). Farmateka 2010; 13: 87-95. Russian (Леонова М.В., Белоусов Ю.Б., Штейнберг Л.Л. и др. Анализ фармакотерапии артериальной гипертонии по результатам исследования ПИФАГОР III (опрос пациентов с АГ). Фарматека 2010; 13: 87-95).

2. Liebson P.R., Grandits G.A., Dianzumba S. et al. Comparison of five antihypertensive monotherapies and placebo for change in left ventricular mass in patients receiving nutritional-hygienic therapy in the Treatment of Mild Hypertension Study (TOMHS). Circulation 1995;91(3):698-706.

3. Wright J.T. Jr., Harris-Haywood S., Pressel S. et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2008;168(2):207-17.

4. Zanchetti A., Julius S., Kjeldsen S. et al. Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial. J Hypertens 2006;24(11):2163-8.

5. Collier D.J., Poulter N.R., Dahlöf B. et al. Impact of amlodipine-based therapy among older and younger patients in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA). J Hypertens 2011;29(3):583-91.

6. Weder A.B. ACCOMPLISH trial findings: combination benazepril-amlodipine or hydrochlorothiazide is effective for treating hypertension. Commentary. Postgrad Med 2009;121(2):199-201.

7. Pitt B., Byington R.P., Furberg C.D. et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation 2000;102(13):1503-10.

8. Jørgensen B., Simonsen S., Endresen K. et al. Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CA-PARES). J Am Coll Cardiol 200;35(3):592-9.

9. Brener S.J., Ivanc T.B., Poliszczuk R. et al. Antihypertensive therapy and regression of coronary artery disease: insights from the Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT) and Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sono-graphic Evaluation (NORMALISE) trials. Am Heart J 2006;152(6):1059-63.

10. Hernaґndez R.H., Armas-Hernaґndez M.J., Zafar H.I., Armas-Padilla M.C. Calcium antagonists and atherosclerosis protection in hypertension. Am J Ther 2003; 10(6): 409-414.

11. Mason R.P., Rhodes DG, Herbette LG. Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with biological membranes. J Med Chem 1991; 34(3): 869-877.

12. Phillips J.E., Mason R.P. Inhibition of oxidized LDL aggregation with a charged calcium antagonist am-lodipine: role of electrostatic interactions. Atherosclerosis 2003; 168(2): 239-244.

13. Mason R.P., Walter M.F., Trumbore M.W. et al. Membrane antioxidant effects of the charged dihydropyridine calcium antagonist amlodipine. J Mol Cell Cardiol 1999; 31(1): 275-281.

14. Zhang X.-P., Xu X., Nasjletti A., Hintze T.H. Amlodipine enhances NO production induced by an ACE inhibitor through a kinin-mediated mechanism in canine coronary microvessels. J Cardiovasc Pharmacol 2000; 35: 195-202.

15. Xu B., X-h L., Lin G. et al. Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide and kinin-dependent mechanism. Br J Pharmacol 2002; 36: 375-382.

16. Goldmann S., Stoltefuss J., Born L. Determination of the absolute configuration of the active amlodipine enantiomer as (–)-S: a correction. J Med Chem 1992; 35: 3341-3344.

17. Zhang X.-P., Loke K.E., Mital S. et al. Paradoxical release of nitric oxide by an L-type calcium channel antagonist, the R-enantiomer of amlodipine. J Cardiovasc Pharmacol 2002; 39: 208-214.

18. Zhang X.-P., Mital S., Hintze T.H. Angiotensin AT2 and AT4 receptor blockade prevents amlodipine and its R-enantiomer stimulated endothelial nitric oxide production (Abstract). Circulation 2001; 104(suppl II): II–33.

19. Mital S., Magneson A., Loke K.E. et al. Simvastatin acts synergistically with ACE inhibitors or amlodipine to decrease oxygen consumption in rat hearts. J Cardiovasc Pharmacol 2000; 36: 248-254.

20. Mason R.P., Marche P., Hintze T.H. Novel vascular biology of third-generation L-type calcium channel antagonists. Arterioscler Thromb Vasc Biol 2003; 23: 2155-2163.

21. Stepien O., Gogusev J., Zhu D.-L. et al. Amlodipine inhibition of serum-, thrombin-, or fibroblast growth factor-induced vascular smooth-muscle cell proliferation. J Cardiovasc Pharmacol 1998; 31: 786-793.

22. Roth M., Eickelberg O., Köhler E. et al. Ca2+ channel blockers modulate metabolism of collagens within the extracellular matrix. Proc Natl Acad Sci 1996; 93: 5478-5482.

23. Luksa J., Josic D., Kremser M. et al. Pharmacokinetic behaviour of R-(+)- and S-(–)-amlodipine after single enantiomer administration. J Chromatogr B Biomed Appl 1997; 703: 185-193.

24. Park J.Y., Kim K.A., Park P.W. et al. Pharmacokinetic and pharmacodynamic characteristics of a new S-amlodipine formulation in healthy Korean male subjects: a randomized, open-label, two-period, comparative, crossover study. Clin Ther 2006; 28:1837-1847.

25. Kim B.-H., Kim J.-R., Kim M.-G. et al. Pharmacodynamic (hemodynamic) and pharmacokinetic comparisons of S-amlodipine gentisate and racemate amlodipine besylate in healthy korean male volunteers: two double-blind, randomized, two-period, two-treatment, two-sequence, double-dummy, single-dose crossover studies. Clin Ther 2010; 32 (1): 193-205.

26. Thacker H.P. S-amlodipine – the 2007 clinical review. J Indian Med Assoc 2007; 105(4): 180 180-2, 184, 186 passim.

For citation:

Leonova M.V. CONTEMPORARY SIGHT AT AMLODIPINE AND NEW DRUGS OF S-AMLODIPINE. Rational Pharmacotherapy in Cardiology. 2011;7(2):227-230. (In Russ.)

Views: 851

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)