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Calcium channel antagonists part V: Second-generation agents

  • Calcium Channel Modulation
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Summary

Second-generation agents include new dihydropyridines, such as amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, and nitrendipine. Verapamil-like agents include tiapamil, gallopamil, and anipamil. Among the diphenylalkylamines, bepridil is of special interest. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. From all these agents will be selected those that are longer-acting and provide higher vascular selectivity.

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References

  1. Faulkner JK, McGibney D, Chasseaud LF, et al. The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol 1986; 22:21–25.

    Google Scholar 

  2. Burges RA, Gardiner DG, Gwilt M, et al. Calcium channel blocking properties of amlodipine in vascular smooth muscle and cardiac muscle in vitro: Evidence for voltage modulation of vascular dihydropyridine receptors. J Cardiovasc Pharmacol 1987; 9:110–119.

    Google Scholar 

  3. Rigby JW, Greengrass PM, Gardiner DG, et al. Interaction of amlodipine with calcium channel binding sites (abstr). Cardiovasc Drugs Ther 1987; 1:281.

    Google Scholar 

  4. Silke B, Jackson NC, Frais MA, et al. Haemodynamic and anti-anginal effects of amlodipine in ischaemic heart disease (abstr). Ann NY Acad Sci (in press).

  5. Lee P, Jackson NC, Cocco G, et al. A dose response study of amlodipine in stable angina (abstr). Cardiovasc Drugs Ther 1987; 1:261.

    Google Scholar 

  6. Frick MH: Amlodipine once daily in the treatment of hypertension (abstr). Cardiovasc Drugs Ther 1987; 1:238.

    Google Scholar 

  7. Maclean D, Mitchell ET, Wilcox RG. A double-blind crossover comparison of amlodipine or placebo added to captopril in moderate to severe hypertension (abstr). Cardiovasc Drugs Ther 1987; 1:263.

    Google Scholar 

  8. Ljung B: Vascular selectivity of felodipine. Drugs 1985; 29(Suppl 2):46–58.

    Google Scholar 

  9. Tweddel AC, Hutton I. Felodipine in ventricular dysfunction. Eur Heart J 1986; 7:54–60.

    Google Scholar 

  10. Timmis AD, Smyth P, Kenny JF, et al. Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure. Br Heart J 1984; 52:314–320.

    Google Scholar 

  11. Binetti G, Pancaldi, Giovanelli N, et al. Hemodynamic effects of felodipine in congestive heart failure. Cardiovasc Drugs Ther 1987; 1:161–167.

    Google Scholar 

  12. Kassis E, Amtorp O. Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure. Circulation 1987; 75:1204–1213.

    Google Scholar 

  13. Tan LB, Murray RG, Littler WA. Felodipine in patients with chronic heart failure: Discrepant haemodynamic and clinical effects. Br Heart J 1987; 58:122–128.

    Google Scholar 

  14. Dunselman PHJM, Scaf AHJ, Kuntze CEE, et al. Interaction between felodipine and digoxin in patients with congestive heart failure (abstr). Cardiovasc Drugs Ther 1987; 1:231.

    Google Scholar 

  15. Aberg H, Lindsjo M, Morlin B. Comparative trial of felodipine and nifedipine in refractory hypertension. Drugs 1985; 29(Suppl 2):117–123.

    Google Scholar 

  16. Katzman PL, Hulthen UL, Hokfelt B: Catecholamines, renin-angiotensin-aldosterone, and cardiovascular response during exercise following acute and long-term calcium antagonism with felodipine in essential hypertension. J Cardiovasc Pharmacol 1987; 10:439–444.

    Google Scholar 

  17. Hansson BG, Lyngstam O, et al. Antihypertensive effect of felodipine combined with β-blockade. A comparison between 2 and 3 daily dosages. Drugs 1985; 29 (Suppl 2):131–136.

    Google Scholar 

  18. Emanuelsson H, Hjalmarson A, Holmberg S, et al. Effects of felodipine on pacing-induced angina pectoris. J Cardiovasc Pharmacol 1986; 8:500–506.

    Google Scholar 

  19. Culling W, Ruttley MSM, Sheridan DJ. Acute haemodynamic effects of delodipine during beta-blockade in patients with coronary artery disease. Br Heart J 1984; 52:431–434.

    Google Scholar 

  20. Freeling R, Harvard Davis R, Goves JR, et al. Control of hypertension in elderly patients with felodipine and metopropol: A double-blind, placebo-controlled clinical trial. Br J Clin Pharmacol 1987; 24:459–464.

    Google Scholar 

  21. Taylor SH, Jackson NC, Allen J, et al. Efficacy of a new calcium antagonist PN 200–110 (Isradipine) in angina pectoris. Am J Cardiol 1987; 59:123B-129B.

    Google Scholar 

  22. Parker JO, Enjalbert M, Bernstein V. Efficacy of the calcium antagonist isradipine in angina pectoris. Cardiovasc Drugs Ther (in press).

  23. Greenberg B, Siemienczuk D, Broudy D. Hemodynamic effects of PN 200–110 (Isradipine) in congestive heart failure. Am J Cardiol 1987; 59:70B-74B.

    Google Scholar 

  24. Broudy DR, Greenberg BHm Siemienczuk D. Beneficial effects of the calcium antagonist PN 200–110 in patients with congestive heart failure. J Cardiovasc Pharmacol 1987; 10:190–195.

    Google Scholar 

  25. Davidov ME, Gonasun LA. Safety and efficacy of isradipine (PN 200-110), a new calcium antagonist in the treatment of essential hypertension (abstr). Ann NY Acad Sci (in press).

  26. Ventura HO, Messerli FH, Oigman W, et al. Immediate hemodynamic effects of a new calcium-channel blocking agent (nitrendipine) in essential hypertension. Am J Cardiol 1983; 51:783–786.

    Google Scholar 

  27. Daniels AR, Opie LH. Effect of slow-release nifedipine on glucose tolerance. In: Lichtlen PR, ed. Sixth International Adalat R Symposium. Amsterdam: Excerpta Medica, 1986; 495–496.

    Google Scholar 

  28. Weinstein DB, Heider JG: Antiatherogenic properties of calcium antagonists. Am J Cardiol 1987; 59:163B-172B.

    Google Scholar 

  29. Pool PE, Seagren SC, Salel AF. Isradipine in the treatment of angina pectoris. Cardiovascular Rev Rep 1987; Special Suppl:13.

  30. Graham DJM, Dow RJ, Hall DJ, et al. The metabolism and pharmacokinetics of nicardipine hydrochloride in man. Br J Clin Pharmacol 1985; 20:23S-28S.

    Google Scholar 

  31. Takenaka T, Asano M, Shiono K, et al. Cardiovascular Pharmacology of nicardipine in animals. Br J Clin Pharmacol 1985; 20:7S-22S.

    Google Scholar 

  32. Visser CA, Koolen JJ, Van Wezel H, et al. Hemodynamics of nicardipine in coronary artery disease. Am J Cardiol 1987; 59:9J-12J.

    Google Scholar 

  33. Subramanian VB. Calcium antagonists in chronic stable angina pectoris. Amsterdam: Excerpta Medica, 1983, 97–116, 152–156, 217–229.

    Google Scholar 

  34. Scheidt S, LeWinter MM, Hermanovich J, et al. Efficacy and safety of nicardipine for chronic, stable angina pectoris: A multicenter randomized trial. Am J Cardiol 1986; 58:715–721.

    Google Scholar 

  35. Thomassen A, Bagger JP, Nielsen TT, et al. Metabolic and hemodynamic effects of nicardipine during pacing-induced angina pectoris. Am J Cardiol 1987; 59:219–224.

    Google Scholar 

  36. Khurmi NS, Raftery EB. Comparative effects of prolonged therapy with four calcium ion antagonists (diltiazem, nicardipine, tiapamil and verapamil) in patients with chronic stable angina pectoris. Cardiovasc Drugs Ther 1987; 1:81–87.

    Google Scholar 

  37. Gelman JS, Feldman RL, Scott E, et al. Nicardipine for angina pectoris at rest and coronary arterial spasm. Am J Cardiol 1985; 56:232–236.

    Google Scholar 

  38. Hanet C, Rousseau MF, Vincent M-F, et al. Myocardial protection by intracoronary nicardipine administration during percutaneous transluminal coronary angioplasty. Am J Cardiol 1987; 59:1035–1040.

    Google Scholar 

  39. Metra M, Nodari S, Nordio G, et al. Comparison of nicardipine and nifedipine in patients with both stable angina pectoris and systemic hypertension: A chronic study (abstr). Ann NY Acad Sci (in press).

  40. Riew KD, Kubo SH, Cody RJ. The direct vasodilator effect of nicardipine and its relationship to basal sympathetic tone in patients with chronic congestive heart failure (abstr). Ann NY Acad Sci (in press).

  41. Ryman KS, Kubo SH, Lystash J, et al. Effect of nicardipine on rest and exercise hemodynamics in chronic congestive heart failure. Am J Cardiol 1986; 58:583–588.

    Google Scholar 

  42. Asplund J: Nicardipine hydrochloride in essential hypertension — a controlled study. Br J Clin Pharmacol 1985; 20:120S-124S.

    Google Scholar 

  43. Taylor SH, Silke B, Ahuja RC, et al. Influence of nicardipine on the blood pressure at rest and on the pressor responses to cold, isometric exertion, and dynamic exercise in hypertensive patients. J Cardiovasc Pharmacol 1982: 4:803–807.

    Google Scholar 

  44. Baba T, Boku A, Ishizaki T, et al. Renal effects of nicardipine in patients with mild to moderate essential hypertension. Am Heart J 1986; 111:552–557.

    Google Scholar 

  45. Van Schaick BAM, Van Nistelrooy AEJ, Geyskes GG. Anti-hypertensive and renal effects of nicardipine. Br J Clin Pharmacol 1984; 18:57–63.

    Google Scholar 

  46. Chaignon M, Bellet M, Lucsko M, et al. Acute and chronic effects of a new calcium inhibitor, nicardipine, on renal hemodynamics in hypertension. J Cardiovasc Pharmacol 1986; 8:892–897.

    Google Scholar 

  47. Kolloch R, Stumpe KO, Overlack A. Blood pressure, heart rate and A-V conduction responses to nicardipine in hypertensive patients receiving atenolol. Br J Clin Pharmacol 1985; 20:130S-134S.

    Google Scholar 

  48. Rousseau MF, Van Mechelen EH, Veriter C, et al. Hemodynamic and cardiac effects of nicardipine in patients with coronary artery disease. J Cardiovasc Pharmacol 1984; 6:833–839.

    Google Scholar 

  49. Sheridan DJ, Thomas P. Vascular versus myocardial selectivity of calcium antagonists. J Cardiovasc Pharmacol 1987; 10(Suppl 1):S165-S168.

    Google Scholar 

  50. Towart R. The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine. Circ Res 1981; 48:650–657.

    Google Scholar 

  51. Allen GS, Ahn HS, Preziosi TJ, et al. Cerebral arterial spasm—a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med 1983; 308:619–624.

    Google Scholar 

  52. Gelmers HJ. The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurol Scand 1984;69:232–239.

    Google Scholar 

  53. Gelmers HJ, Gorter K, et al. de Weerdt CJ, et al. New aspects in stroke therapy (abstr). Ann NY Acad Sci (in press).

  54. Nyborg NCB, Mikkelsen EO. Comparison of the inhibitory effects of nifedipine and nimodipine on mechanical responses of isolated rat coronary small arteries. J Cardiovasc Pharmacol 1987;9:519–524.

    Google Scholar 

  55. Kass RS. Nisodipine: A new more selective calcium current blocker in cardiac Purkinje fibers. J Pharmacol Exp Ther 1983;223:446.

    Google Scholar 

  56. Knorr A: The pharmacology of nisoldipine. Cardiovasc Drugs Ther 1987;1:393–402.

    Google Scholar 

  57. Graefe K-H, Ziegler R, Wingender W, et al. Cardiovascular effects of dihydropyridine calcium-channel antagonists and their relation to drug levels in plasma of healthy male volunteers (abstr). Ann NY Acad Sci (in press).

  58. Laederach K, Weidmann P, Lauener F, et al. Comparative acute effects of the calcium channel blockers tiapamil, nisoldipine and nifedipine on blood pressure and some regulatory factors in normal and hypertensive subjects. J Cardiovasc Pharmacol 1986;8:294–302.

    Google Scholar 

  59. Taira N, Takahashi K: Cardiovascular profile of nisoldipine as compared to nifedipine in dogs. In: Hugenholtz PG, Meyer J, eds. Nisoldipine 1987. Berlin: Springer-Verlag, 1987;131–143.

    Google Scholar 

  60. Serruys PW, Suryapranata H, Planellas J, et al. Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics. Am J Cardiol 1985; 56:140–146.

    Google Scholar 

  61. Lopez LM, Rubin MR, Holland JP, et al. Improvement in exercise performance with nisoldipine, a new second generation calcium blocker in stable angina patients, clinical investigations. Am Heart J 1985; 110: 991–996.

    Google Scholar 

  62. Lam J, Chaitman BR, Crean P, et al. A dose-ranging, placebo-controlled, double-blind trial of nisoldipine in effort angina: Duration and extent of antianginal effects. J Am Coll Cardiol 1985; 6:447–452.

    Google Scholar 

  63. Reicher-Reiss H, Vered Z, Goldbourt H, et al. Efficacy of nisoldipine compared with nifedipine in chronic stable angina. In: Hugenholtz PG, Meyer J, eds. Nisoldipine 1987. Berlin: Springer-Verlag, 1987;233–237.

    Google Scholar 

  64. Pedersen TR, Kantor M: Nifedipine three times daily versus nisoldipine once daily in patients with severe effort angina pectoris pretreated with atenolol (abstr). Cardiovasc Drugs Ther 1987; 1:275.

    Google Scholar 

  65. Rosendorff C, Goodman C. Double-blind, double-dummy, cross-over study of the efficacy and safety of nisoldipine (BAY K-5552) versus nifedipine. Curr Ther Res 1985; 37:912–920.

    Google Scholar 

  66. Daniels AR, Opie LH. Monotherapy with the calcium channel antagonist nisoldipine for systemic hypertension and comparison with diuretic drugs. Am J Cardiol 1987; 60:703–707.

    Google Scholar 

  67. Lund-Johansen P, Omvik P: Central hemodynamic changes of calcium antagonists at rest and during exercise in essential hypertension. J Cardiovasc Pharmacol 1987; 10 (Suppl 1):S139-S148.

    Google Scholar 

  68. Catagay M, Frost N, Weiss KH, et al. Assessment of longterm efficacy and tolerability of nisoldipine by the clinical data pool. In: Hugenholtz PG, Meyer J, eds. Nisoldipine 1987. Berlin: Springer-Verlag, 1987;201–210.

    Google Scholar 

  69. Barjon J-N, Rouleau J-L, Bichet D, et al. Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure. J Am Coll Cardiol 1987; 9:622–630.

    Google Scholar 

  70. Kiowski W, Erne P, Pfisterer M, et al. Arterial vasodilator, systemic and coronary hemodynamic effects of nisoldipine in congestive heart failure secondary to ischemic or dilated cardiomyopathy. Am J Cardiol 1987; 59:1118–1125.

    Google Scholar 

  71. Hess P, Lansman JB, Tsien RW. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 1984; 311:538–544.

    Google Scholar 

  72. Muller FB, Bolli P, Erne P, et al. Antihypertensive therapy with long-acting calcium antagonist nitrendipine. J Cardiovasc Pharmacol 1984; 6 (Suppl 7):S1073-S1076.

    Google Scholar 

  73. Scriabine A, Anderson CL, Janis RA, et al. Some recent pharmacological findings with nitrendipine. J Cardiovasc Pharmacol 1984; 6 (Suppl 7):S937-S943.

    Google Scholar 

  74. Kann J, Krol GJ, Raemsch KD, et al. Bioequivalence and metabolism of nitrendipine administered orally to healthy volunteers. J Cardiovasc Pharmacol 1984; 6 (Suppl 7): S968–973.

    Google Scholar 

  75. Franz IW, Wiewel D: Antihypertensive effects on blood pressure at rest and during exercise of calcium antagonists, β-receptor blockers, and their combination in hypertensive patients. J Cardiovasc Pharmacol 1984; 6 (Suppl 7):S1037-S1042.

    Google Scholar 

  76. Muller FB, Bolli P, Erne P, et al. Calcium antagonism—a new concept for treating essential hypertension. Am J Cardiol 1986; 57:50D-53D.

    Google Scholar 

  77. M'Buyamba-Kabangu JR, Lepira B, Fagard R, et al. Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients. Eur J Clin Pharmacol 1986; 29:523–527.

    Google Scholar 

  78. M'Buyamba-Kabangu JR, Fagard R, Linjen P, et al. Calcium entry blockade or beta-blockade in long-term management of hypertension in blacks. Clin Pharmacol Ther 1987; 41:45–54.

    Google Scholar 

  79. Fagan TC, Sternleib C, Vlachakis N. Efficacy and safety comparison of nitrendipine and hydralazine as antihypertensive monotherapy. J Cardiovasc Pharmacol 1984; 6(Suppl 7):S1109-S1113.

    Google Scholar 

  80. Weber MA, Drayer JIM. The calcium channel blocker nitrendipine in single- and multiple-agent antihypertensive regimens: Preliminary report of a multicenter study. J Cardiovasc Pharmacol 1984; 6(Suppl 7):S1077-S1084.

    Google Scholar 

  81. Schoenberger JA, Glasser SP, Ram CVS, et al. Comparison of nitrendipine combined with low-dose hydrochlorothiazide to hydrochlorothiazide alone in mild to moderate essential hypertension. J Cardiovasc Pharmacol 1984; 6(Suppl 7):S1105-S1108.

    Google Scholar 

  82. Salzmann R, Bormann G, Herzig JW, et al. Pharmacological actions of APP 201–533, a novel cardiotonic agent. J Cardiovasc Pharmacol 1985; 7:588–596.

    Google Scholar 

  83. Kirch W, Hutt HJ, Heidmann H, et al. Drug interactions with nitrendipine. J Cardiovasc Pharmacol 1984; 6(Suppl 7):S982-S985.

    Google Scholar 

  84. Olivari MT, Levine TB, Weir EK, et al. Hemodynamic effects of nifedipine at rest and during exercise in primary pulmonary hypertension. Chest 1984; 86:14–19.

    Google Scholar 

  85. Daniels AR, Opie LH: Atenolol plus nifedipine for mild to moderate systemic hypertension after fixed doses of either agent alone. Am J Cardiol 1986; 57:965–970.

    Google Scholar 

  86. Singer DRJ, Markandu ND, Shore AC, et al. Nifedipine and acebutolol in combination for the treatment of moderate to severe essential hypertension. J Hum Hypertens 1987; 1:31–37.

    Google Scholar 

  87. Gould BA, Hornung RS, Mann S, et al. Slow channel inhibitors verapamil and nifedipine in the management of hypertension. J Cardiovasc Pharmacol 1982; 4(Suppl III):S369-S373.

    Google Scholar 

  88. MacGregor GA. Hypertension. In: Krebs R, ed. Treatment of Cardiovascular Diseases by Adalat R (Nifedipine). Stuttgart: Schattauer, 1986;231–258.

    Google Scholar 

  89. Vetrovec GW, Parker VE, Alpert DH. Antianginal efficacy of continuous release nifedipine (N-GITS) (abstr). Ann NY Acad Sci (in press).

  90. Raferty EB. Verapamil SR. Once-Daily Calcium Blockade in Angina and Hypertension. Langhorne: ADIS Press International, 1987.

    Google Scholar 

  91. Kohli RS, Rodrigues EA, Hughes LO, et al. Sustained release verapamil, a once daily preparation: Objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina. J Am Coll Cardiol 1987; 9:615–621.

    Google Scholar 

  92. Brugmann U. Calcium antagonists in hypertension and coronary heart disease. Results of a double-blind, randomized, placebo-controlled study with sustained-release verapamil. In: Rosenthal J, ed. Calcium Antagonists and Hypertension: Current Status. Amsterdam: Excerpta Medica, 1986;209–219.

    Google Scholar 

  93. Buhler FR, Hulthen U, Kiowski W, et al. The place of the calcium antagonist verapamil in antihypertensive therapy. J Cardiovasc Pharmacol 1982; 4:S350-S357.

    Google Scholar 

  94. Taylor SH, Silke B. Continuous blood pressure control with sustained verapamil in essential hypertension. In: Raftery EB, ed. Verapamil SR. Once-Daily Calcium Blockade in Angina and Hypertension. Langhorne: ADIS Press International, 1987;57–62.

    Google Scholar 

  95. Midtbo K, Hals O, van der Meer J, et al. Instant and sustained-release verapamil in the treatment of essential hypertension. Am J Cardiol 1986; 57:59D-63D.

    Google Scholar 

  96. Schwartz JB, Keefe DL, Kirsten E, et al. Prolongation of verapamil elimination kinetics during chronic oral administration. Am Heart J 1982; 104:198–203.

    Google Scholar 

  97. Frishman W, Charlap S, Kimmel B, et al. Twice-daily administration of oral verapamil in the treatment of essential hypertension. Arch Intern Med 1986: 146:561–565.

    Google Scholar 

  98. Norris RJ, Brooks SG. Pharmacokinetics of a sustained release formulation of verapamil in young and elderly adults. In: Raftery EB, ed. Verapamil SR. Once-Daily Calcium Blockade in Angina and Hypertension. Langhorne: ADIS Press International, 1987;38–46.

    Google Scholar 

  99. Kellaway IW. The development and clinical implications of sustained release formulations. In: Raftery EB, ed. Verapamil SR. Once-Daily Calcium Blockade in Angina and Hypertension. Langhorne: ADIS Press International, 1987;30–37.

    Google Scholar 

  100. Weiner DA, Cutler SS, Klein MD. Efficacy and safety of sustained-released diltiazem in stable angina pectoris. Am J Cardiol 1986: 57:6–9.

    Google Scholar 

  101. Osterrieder W: Inhibition of the fast Na+ inward current by the CA2+ channel blocker tiapamil. J Cardiovasc Pharmacol 1986; 8:1101–1106.

    Google Scholar 

  102. Eichler HG, Mabin TA, Commerford PJ, et al. Tiapamil, a new calcium antagonist: Hemodynamic effects in acute myocardial infarction. Circulation 1985; 71:770–786.

    Google Scholar 

  103. Khurmi NS, O'Hara MJ, Bowles MJ, et al. Randomized double-blind comparison of gallopamil and propranolol in stable angina pectoris. Am J Cardiol 1984; 53:684–688.

    Google Scholar 

  104. Hopf R, Drews H, Kaltenbach M. Anti-anginal effect of gallopamil as compared with nifedipine. In: Kaltenbach M, Hopf R, eds. Gallopamil. Pharmacological and Clinical Profile of a Calcium Antagonist. Berlin: Springer-Verlag, 1984;123–131.

    Google Scholar 

  105. Maddalena F, Casiglia E, Padrini R, et al. Gallopamil in unstable angina pectoris (abstr). Ann NY Acad Sci (in press).

  106. Raschack M. Prolonged cardioprotective effects of anipamil, a new calcium antagonist (abstr). Eur Heart J 1984; 5:10.

    Google Scholar 

  107. Dies R, Hahn KJ. The blood pressure lowering effect of anipamil, in mild to moderate hypertension (abstr). Ann NY Acad Sci (in press).

  108. Ferrari R, Ceconi C, Curello S, et al, Long lasting protective effect of anipamil, a new calcium entry blocker, against myocardial ischemia and reperfusion damage (abstr), Ann NY Acad Sci (in press).

  109. Nawrath H, Raschack M. (-)-Devapamil decreases tension and calcium-45 uptake in smooth muscle preparations from rat aorta (abst), Ann NY Acad Sci (in press).

  110. Au TLS, Curtis MJ, Walker MJA. Effects of (-), (+), and (+) verapamil on coronary occlusion-induced mortality and infarct size. J Cardiovasc Pharmacol 1987; 10:327–331.

    Google Scholar 

  111. Thandroyen FT, Higginson L, Opie LH, et al. The influence of verapamil and its isomers on vulnerability to ventricular fibrillation during acute myocardial ischemia and adrenergic stimulation in isolated rat heart. J Mol Cell Cardiol 1986; 18:645–649.

    Google Scholar 

  112. Spedding M. Calcium antagonist subgroups. Trends Pharmaceut Sci 1985; 6:109–114.

    Google Scholar 

  113. Spedding M. Activators and inactivators of Ca++ channels: New perspectives. J Pharmacol 1985; 16:319–343.

    Google Scholar 

  114. Spedding M, Berg C. Interactions between a “calcium channel agonist”, Bay K8644, and calcium antagonists differentiate calcium antagonist subgroups in K+-depolarized smooth muscle. Naunyn-Schmiedebergs Arch Pharmacol 1984; 328:69–75.

    Google Scholar 

  115. Terada K, Ohya Y, Kitamura K, et al. Actions of flunarizine, a Ca2+ antagonist, on ionic currents in fragmented smooth muscle cells of the rabbit small intestine. J Pharmacol Exp Ther 1987; 240:978–983.

    Google Scholar 

  116. Kato R, Singh BN. Effects of bepridil on the electrophysiologic properties of isolated canine and rabbit myocardial fibers. Am Heart J 1986; 111:271–279.

    Google Scholar 

  117. Perelman MS, McKenna WJ, Rowland E, et al. A comparison of bepridil with amiodarone in the treatment of established atrial fibrillation. Br Heart J 1987; 58:339–344.

    Google Scholar 

  118. Roy D, Montigny M, Klein GJ, et al. Electrophysical effects and long-term efficacy of bepridil for current supraventricular tachycardias. Am J Cardiol 1987; 59:89–92.

    Google Scholar 

  119. Remme WJ, van Hoofenhuyze DCA, Kraus XH, et al. Dose related coronary and systemic haemodynamic effects of intravenous bepridil in patients with coronary artery disease. Eur Heart J 1987; 8:130–140.

    Google Scholar 

  120. Shapiro W, DiBianco R, Thadani U, et al. Comparative efficacy of 200, 300 and 400 mg of bepridil for chronic stable angina pectoris. Am J Cardiol 1985; 55:36C-42C.

    Google Scholar 

  121. Hill JA, O'Brien JT, Scott E, et al. Effects of bepridil on exercise tolerance in chronic stable angina: A double-blind, randomized, placebo-controlled, crossover trial. Am J Cardiol 1984; 53:679–683.

    Google Scholar 

  122. Pflugfelder PW, Humen DP, O'Brien PA, et al. Comparison of bepridil with nadolol for angina pectoris. Am J Cardiol 1987; 59:1283–1288.

    Google Scholar 

  123. Frishman WH, Charlap S, Farnham DJ, et al. Combination propranolol and bepridil therapy in stable angina pectoris. Am J Cardiol 1985; 55:43C-49C.

    Google Scholar 

  124. Hill JA, Pepine CJ. Effects of bepridil on the resting electrocardiogram. Int J Cardiol 1984; 6:319–323.

    Google Scholar 

  125. Surawicz B, Knoebel SB, Long QT: Good, bad or indifferent? J Am Coll Cardiol 1984; 4:398–413.

    Google Scholar 

  126. Shapiro W, Narahara KA, Park J. The effects of lidoflazine on exercise performance and thallium stress scintigraphy in patients with stable angina pectoris. Circulation 1982; 65:1–43.

    Google Scholar 

  127. Hanley SP, Hampton JR. Ventricular arrhythmias associated with lidoflazine: Side-effects observed in a randomized trial. Eur Heart J 1983; 4:889–893.

    Google Scholar 

  128. Keren G, Tepper D, Butler B, et al. Studies on the possible mechanisms of lidoflazine arrhythmogenicity. J Am Coll Cardiol 1984; 4:742–747.

    Google Scholar 

  129. Wauquier A, Fransen J, Clincke G, et al. Calcium entry blockers as cerebral protecting agents. In: Godfraind T, et al., eds. Calcium Entry Blockers and Tissue Protection. New York: Raven Press, 1985; 163–172.

    Google Scholar 

  130. Newberg LA, Steen PA, Milde JH, et al. Failure of flunarizine to improve cerebral blood flow or neurologic recovery in a canine model of complete cerebral ischemia. Stroke 1984; 15:666–671.

    Google Scholar 

  131. Itoh T, Satoh S, Ishimatsu T, et al. Mechanisms of flunarizine-induced vasodilation in the rabbit mesenteric artery. Circ Res 1987; 61:446–454.

    Google Scholar 

  132. Silver PJ, Sulkowski TS, Lappe RW, et al. Wy-46,300 and Wy-46,531: Vascular smooth muscle relaxant/antihypertensive agents with combined Ca2+ antagonist/myosin phosphorylation inhibitory mechanisms. J Cardiovasc Pharmacol 1986; 8:1168–1175.

    Google Scholar 

  133. Bayer R, Martini E, Heckelmann F. Calcium channel-independent action of fendiline in vascular smooth muscle (abstr). J Mol Cell Cardiol 1987; 19 (Suppl III):S4.

    Google Scholar 

  134. Marshall RJ, Winslow E, Relevance of intracellular actions of Ca++-antagonists in the treatment of coronary heart disease (abstr). J Mol Cell Cardiol 1987; 19(Suppl III):S57.

    Google Scholar 

  135. Belz GG. Fendiline: Clinical pharmacological profile of a Ca++-CaM-antagonist (abstr). J Mol Cell Cardiol 1987; 19 (Suppl III):S5.

  136. Erwes H. Fendiline in the treatment of coronary heart disease (abstr). J Mol Cell Cardiol 1987; 19 (Suppl III):S21.

    Google Scholar 

  137. Thandroyen FT, McCarthy J, Burton K, et al. Ryanodine and caffeine prevent ventricular arrhythmias during acute myocardial ischemia and reperfusion in rat heart. Circ Res (in press).

  138. Shibata S, Wakabayashi S, Satake N, et al. Mode of vasorelaxing action of 5-[3][2-(3,4-dimethoxyphenyl)-ethyl]amino]-1-oxopropyl]-2,3,4,5-tetrahydro-1,5-benzothiazepine fumarate (KT-362), a new intracellular calcium antagonist. J Pharmacol Exp Ther 1987; 240:16–22.

    Google Scholar 

  139. Edgar B, Hoffman KJ, Lundborg P, et al. Absorption, distribution and elimination of felodipine in man. Drugs 1985; 29(Suppl 2):9–15.

    Google Scholar 

  140. Raemsch KD, Luecker PW, Wetzelsberger N. Pharmacokinetics of intravenously and orally administered nimodipine (abstr). Clin Pharmacol Ther 1987; 41:216.

    Google Scholar 

  141. Lasseter KC, Shamblen EC, Lettieri J, et al. Dose-proportional pharmacokinetics of nisoldipine in healthy volunteers (abstr). Clin Pharmacol Ther 1987; 41:234.

    Google Scholar 

  142. Pasanisi F, Meredith PA, Reid JL. The pharmacodynamics and pharmacokinetics of a new calcium antagonist nisoldipine in normotensive and hypertensive subjects. Eur J Clin Pharmacol 1985; 29:21–24.

    Google Scholar 

  143. Stieren B, Buhler V, Hege, et al. Pharmacokinetics and metabolism of gallopamil. In: Kaltenbach M, Hopf R, eds. Gallopamil. Pharmacological and Clinical Profile of a Calcium Antagonist. Berlin: Springer-Verlag, 1984;88–93.

    Google Scholar 

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Opie, L.H. Calcium channel antagonists part V: Second-generation agents. Cardiovasc Drug Ther 2, 191–203 (1988). https://doi.org/10.1007/BF00051234

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