Investigational Drug Information

Flaim SF Flaim KE Zelis R . Diltiazem: Lack of myocardial beta-adrenergic receptor-binding capacity. Pharmacology 1980; 21: 306–12.

Flaim SF Tarka LA Flaim KE . Binding capacity of diltiazem to myocardial beta adrenergic receptors. Clin Res 1979; 27: 165A.

Sato M Nagao T Yamaguchi I . Pharmacological studies on a new 1,5-benzothiazepine derivative (CRD-401). I. Cardiovascular actions. Arzneim Forsch 1971; 21: 1338–43.

Nagao T Sato M Nakajima H . Studies on a new 1,5-benzothiazepine derivative (CRD-401). II. Vasodilator actions. Jpn J Pharmacol 1972; 22: 1–10.

Nakajima H Hoshiyama M Yamashita K . Effect of diltiazem on electrical and mechanical activity of isolated cardiac ventricular muscle of guinea pig. Jpn J Pharmacol 1975; 25: 383–92.

Nabata H . Effects of calcium-antagonistic coronary vasodilators on myocardial contractility and membrane potentials. Jpn J Pharmacol 1977; 27: 239–49.

Nakajima H Hoshiyama M Yamashita K . Electrical and mechanical responses to diltiazem in potassium depolarized myocardium of the guinea pig. Jpn J Pharmacol 1976; 26: 571–80.

Saikawa T Nagamoto Y Arita M . Electrophysiologic effects of diltiazem, a new slow channel inhibitor, on canine cardiac fibers. Jpn Heart J 1977; 18: 235–45.

Arita M Saikawa T Nagamoto Y . Effects of diltiazem hydrochloride (CRD-401) on action potentials of canine heart muscle. Jpn J Clin Exp Med 1975; 52: 2156.

Nagao T Matlib MA Franklin D . Effects of diltiazem, a calcium antagonist, on regional myocardial function and mitochondria after brief coronary occlusion. J Mol Cell Cardiol 1980; 12: 29–43.

Weishaar R Ashikawa K Bing RJ . Effect of diltiazem, a calcium antagonist, on myocardial ischemia. Am J Cardiol 1979; 43: 1137–43.

Weishaar RE Bing RJ . The beneficial effect of a calcium channel blocker, diltiazem, on the ischemic-reperfused heart. J Mol Cell Cardiol 1980; 12: 993–1009.

Nakajima H Nosaka K Hoshiyama M . Effects of diltiazem on the positive inotropic and vasoconstrictor responses to ouabain in vitro. Pharmacology 1977; 27: 910–4.

Yabe Y Abe H Yoshimura S . Effect of diltiazem on coronary hemodynamics and its clinical significance. Jpn Heart J 1979; 20: 83–93.

Takeda K Nakagawa Y Katano Y . Effects of coronary vasodilators on large and small coronary arteries of dogs. Jpn Heart J 1977; 18: 92–101.

Cavero I Boudot JP Lefevre-Borg F . Pharmacological evaluation of diltiazem and its desacetylated metabolite in several animal species: II. Hemodynamic effects of diltiazem and desacetydiltiazem in pentobarbital anesthetized dogs. In: Bing RJ , ed. New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium '78 (No. 487). Amsterdam: Elsevier North Holland, 1979: 71–80.

Nagao T Sato M Nakajima H . Studies on a new 1,5-benzothiazepine derivative (CRD-401). IV. Coronary vasodilating effect and structure-activity relationship. Chem Pharm Bull 1973; 21: 92–7.

Okada K Yamaguchi Y Innami H . Effect on CRD-401, a coronary vasodilator, or systemic blood flow distribution. Jpn J Anaesth 1972; 21: 781–6.

Sato M Murata S Narita H . Hypotensive effects of diltiazem hydrochloride in the normotensive, spontaneously hypertensive and renal hypertensive rats. Nippon Yakurigaku Zasshi 1979; 75: 99–106.

Sakurai T Kurita T Nagano S . Antihypertensive, vasodilating and sodium diuretic actions of d-cis-isomer of benzothiazepine derivative (CRD-401). Acta Urol Jpn 1972; 18: 695.

Mori M Koiwaya Y Okamatsu S . The effects of CRD-401 on acute myocardial ischemia. Jpn Circ J 1976; 40: 472–3.

Millard RW . Changes in cardiac mechanics and coronary blood flow of regionally ischemic porcine myocardium induced by diltiazem. Chest 1980; 78 (July suppl): 193–9.

Nagao T Murata S Sato M . Effects of diltiazem (CRD-401) on developed coronary collaterals in the dog. Jpn J Pharmacol 1975; 25: 281–8.

Franklin D Millard RW Nagao T . Responses of coronary collateral flow and dependent myocardial mechanical function to the calcium antagonist, diltiazem. Chest 1980; 78 (July suppl): 200–4.

Walsh R Badke F O'Rourke R . Differential effects of diltiazem and verapamil on left ventricular performance in conscious dogs. Circulation 1979; 60 (suppl II):15.

Walsh R Badke F O'Rourke R . Differential effects of intracoronary calcium antagonists on regional shortening in conscious dogs. Circulation 1980; 62 (suppl III):10.

Walsh R Badke F O'Rourke R . Differential effects of intracoronary calcium antagonists on regional shortening in conscious dogs. Am Heart J 1981; 102: 341–50.

Flaim SF Zelis R . Diltiazem: Systemic coronary vasodilator without negative inotropic effects on conscious rats. Fed Proc 1980; 39: 2335.

Nakaya H Schwartz A Millard RW . Cardiac effects of equihypotensive doses of calcium channel blocking agents in conscious dogs (abstract). Circulation 1981; 64: 167.

Ishikawa H Matsushima A Matsui H . Effects of diltiazem hydrochloride (CRD-401) on hepatic, superior mesenteric and femoral hemodynamics. Arzneim Forsch 1978; 28: 400–2.

Ito Y Kuriyama H Suzuki H . The effects of diltiazem (CRD-401) on the membrane and mechanical properties of vascular smooth muscles of the rabbit. Br J Pharmacol 1978; 64: 503–10.

Yamaguchi I Ikezawa K Takada T . Studies on a new 1,5-benzothiazepine derivative (CRD-401). VI. Effects on renal blood flow and renal function. Jpn J Pharmacol 1974; 24: 511–22.

Tsuyusaki T Noro C Yabata Y . Clinical study on long term oral administration of diltiazem hydrochloride (CRD-401). Jpn J Clin Exp Med 1976; 53: 247.

Ueda S Ikegami K Sakanashi M . Effects of prostaglandin E₁ on isolated dog renal artery. Urology 1979; 14: 646–51.

Ishikawa H Matsushima M Matsui H . Effects of diltiazem hydrochloride (CRD-401) on renal hemodynamics of dogs. Arzneim Forsch 1978; 28: 402–6.

Hirakawa M Shiwaku Y Aji T . Experimental and clinical studies on the diuretic action of CRD-401. Anesth J Resusc 1975; 11: 159–62.

Yamaguchi I Ikezawa K Murata S . Hypotensive effects of diltiazem in DOCA/saline hypertensive rats. Nippon Yakurigaku Zasshi 1979; 75: 191–9.

Sata R Tanaka S Sawada S . Vascular action of angiotensin. Effect of diltiazem (CRD) calcium antagonist on the response to angiotensin and noradrenaline in normotensive and Goldblatt-type hypertensive rats. Jpn Circ J 1976; 40: 522.

Osada T Kajiwara N Kobayashi Y . The inhibition of hypertension and the historical changes in SHR treated with diltiazem. Jpn Heart J 1979; 20: 745.

Osada T Kijiwara N Kobayashi Y . The inhibition of hypertension and the changes of the humoral factors in spontaneously hypertensive rat treated with diltiazem. Jpn Heart J 1980; 21: 581.

Bush L Yuk-Ping L Shlafer M . Protective effects of diltiazem during myocardial ischemia in isolated cat hearts. J Pharmacol Exp Ther 1981; 218: 653–61.

Kinoshita M Takayama Y Kato S . Protection of coronary reperfusion injury by a calcium antagonist. Jpn Circ J 1980; 44: 461–6.

Schwartz A Grupp G Millard R . Calcium-channel blockers: Possible mechanisms of protective effects on the ischemic myocardium. Am J Physiol 1982: in press.

Vaghy P Matlib M Szekeres L . Protective effects of verapamil and diltiazem against inorganic phosphate induced impairment of oxidative phosphorygation of isolated heart mitochondria. Biochem Pharm 1981; 30: 2603–10.

Flaim SF Copenhaver GL Whitesell LF . Effect of diltiazem pretreatment to reduce experimental myocardial infarct size in rat. Clin Res 1980; 28: 611A.

Bush LR Ramson JL Ash JL . Effects of diltiazem from temporary coronary artery occlusion in dogs. J Cardiovasc Pharm 1982: in press.

Miura M Kanazawa T . Effect of diltiazem on the infarct size in closed-chest anesthetized dogs. In: Bing RJ , ed. New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium '78 (No. 487). Amsterdam: Elsevier North Holland, 1979: 16–24.

Clusin WT Bristow MR Jaillon P . Diltiazem and reduced serum ionized calcium both retard ventricular fibrillation following coronary ligation. Clin Res 1981; 29: 181.

Sakuma M Yoshikawa M Sato Y . The whole body autoradiographic studies on the distribution of ¹⁴C-labeled new 1,5-benzothiazepine derivative (¹⁴D-CRD-401) in mice. Chem Pharm Bull 1971; 19: 995–1005.

Meshi T Sigihara J Sato Y . Metabolic fate of d-cis-3-acetoxy-5[2-(dimethylamino)ethyl]-2,3-dihydro-2-(p-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one hydrochloride (CRD-401). Chem Pharm Bull 1971; 19: 1546–56.

Piepho RW Bloedow DC Lacz JP . Pharmacokinetics of diltiazem in selected animal species. Am J Cardiol 1982; 49: 525–8.

Kinney E Moskowitz RM Zelis RF . The pharmacokinetics and pharmacology of oral diltiazem in normal volunteers. J Clin Pharmacol 1981; 21: 337–42.

Bourassa MG Cote P Theroux P . Hemodynamics and coronary flow following diltiazem administration in anesthetized dogs and in humans. Chest 1980; 78 (July suppl): 224–30.

Yamaguchi H Nagasaki F Nakanishi S . Effects of diltiazem on coronary artery and hemodynamics. In: Bing RJ , ed. New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium '78 (No. 487). Amsterdam: Elsevier North Holland, 1979: 204–13.

Tabau JF Cote P Bourassa MG . Systemic and coronary hemodynamic effects of intravenous diltiazem in patients with coronary artery disease. Am J Cardiol 1980; 45: 439.

Yasue H Nagao M Omote S . Coronary arterial spasm and Prinzmetal's variant form of angina induced by hyperventilation and Tris-buffer infusion. Circulation 1978; 58: 56–62.

Waters DD Szlachcic J Theroux P . Ergonovine testing to detect spontaneous remission of variant angina during long-term treatment with calcium antagonist drugs. Am J Cardiol 1981; 47: 179–84.

Hossack KF Bruce RA . Divergent effects of diltiazem in patients with exertional angina. Am J Cardiol 1982; 49: 538–46.

Rosenthal SJ Baim DS Lamb IH . Effect of diltiazem hydrochloride capsules on cardiac hemodynamic and electrocar-diographic function. Curr Ther Res 1980; 28: 319–25.

Debaisieux JC Theroux P Waters DD . Hemodynamic effects of nifedipine and diltiazem after an acute myocardial infarction. Circulation 1979; 60 (suppl II):82.

Kinoshita M Kusukawa R Shimono Y . Effects of diltiazem hydrochloride on renal hemodynamics and urinary electrolyte excretion. Jpn Circ J 1978; 42: 553–60.

Cherrier AF . Hemodynamic effects of the association of diltiazem with beta-blockers. Data on file, Marion Laboratories, Kansas City, MO 64137.

Medvedowsky JL Barnay AC Gauet DM . Electrophysiological study of interactions between diltiazem and propranolol, pindolol and amiodarone. Data on file, Marion Laboratories, Kansas City, MO 64137.

McGraw BF Gitomer SL Walker SD . Post-marketing experience with diltiazem hydrochloride in 3913 patients (abstract). Drug Intell Clin Pharm 1981; 15: 481.

Takagi M Tsuruha Y Shiotsu H . Effect of diltiazem hydrochloride on the atrioventricular conduction. Heart 1978; 10: 298.

Mitchel LB Jutzy KR Lewis SJ . Intracardiac electrophysiologic study of intravenous diltiazem and the combination of intravenous diltiazem and digoxin in man. Am Heart J 1982; 103: 57–66.

Oyama Y Imai Y Nakaya H . The effects of diltiazem hydrochloride on the cardiac conduction: A clinical study of His bundle electrogram. Jpn Circ J 1978; 42: 1257–64.

Kawai C Konishi T Matsyama E . Comparative effects of three calcium antagonists, diltiazem, verapamil and nifedipine, on the sinoatrial and atrioventricular nodes. Experimental and clinical studies. Circulation 1981; 63: 1035–42.

Pool PE Seagren SC Bonanno JA . The treatment of exercise-inducible chronic stable angina with diltiazem. Chest 1980; 78 (July suppl): 234–8.

Starling MR Crawford MH O'Rourke RA . Beneficial effects of diltiazem on exercise performance in patients with coronary artery disease and angina pectoris. Am J Cardiol 1981; 47: 464.

Hossack KF Bruce RA . Improved exercise performance in persons with stable angina-pectoris receiving diltiazem. Am J Cardiol 1981; 47: 95–101.

Low RI Takeda P Lee G . Enhancement of exercise tolerance by diltiazem-induced calcium blockade in patients with coronary-artery disease. Am Heart J 1981; 101: 713–8.

Hossack KF Poole P Crawford M . Efficacy of diltiazem in effort angina—a multicenter study. Am J Cardiol 1982; 49: 567–72.

Battock DJ Alverez H Chidsey CA . Effects of propranolol and isosorbide dinitrate on exercise performance and adrenergic activity in patients with angina pectoris. Circulation 1969; 34: 157–69.

Dagenais GR Pitt B Ross RS . Exercise tolerance in patients with angina pectoris. Am J Cardiol 1971; 28: 10–16.

Alderman EL Davies RO Crowley JJ . Dose response effectiveness of propranolol for the treatment of angina pectoris. Circulation 1975; 51: 964–75.

Thadani U Parker JO . Propranolol in the treatment of angina pectoris. Circulation 1979; 59: 571–9.

Jackson G Schwartz J Kages RE . Atenolol: Once-daily cardioselective beta blockage for angina pectoris. Circulation 1980; 61: 555–60.

Gionelly RE Goldman RH Triester B . Propranolol in patients with angina pectoris. Ann Intern Med 1967; 67: 1216–25.

Delage F Roulean JR Labelle J . Effects of metoprolol on effort angina during the postprandial state. Clin Pharmacol Ther 1980; 27: 764–8.

Thadani U Fung H Darke AC . Oral isosorbide dinitrate in the treatment of angina pectoris. Circulation 1980; 62: 491–502.

Glancy DL Richter MA Ellis EV . Effect of swallowed isosorbide dinitrate on blood pressure, heart rate and exercise capacity in patients with coronary artery disease. Am J Med 1977; 62: 39–46.

Strauss WE McIntyre KM Parisi AF . Safety and efficacy of diltiazem hydrochloride for stable angina pectoris. Am J Cardiol 1982; 49: 560–6.

DeBacker B Vincke J . A double-blind crossover study, diltiazem versus placebo, in chronic exertional angina. Data on file, Marion Laboratories, Kansas City, MO 64137.

Brechenmacher F Boxho G . Multicenter study of diltiazem and pindolol using a double-blind crossover design. Data on file, Marion Laboratories, Kansas City, MO 64137.

Canicave JC . Double-blind crossover study of diltiazem and acebutolol using exercise testing. Data on file, Marion Laboratories, Kansas City, MO 64137.

Guermonprez JL Blanchard D Lancelin B . Evaluation of diltiazem in stable angina by serial exercise tests. Circulation 1980; 62 (suppl III):296.

Kober G Berlad T Hopf R . The effect of diltiazem and nifedipine on exercise-induced ST-segment depression and heart rate in patients with coronary heart disease. Z Kardiol 1981; 70: 59–65.

Koiwaya Y . The effects of diltiazem hydrochloride on hemodynamics, epicardial unipolar ECG and regional myocardial blood flow in dogs with acute coronary occlusion. Fukuoka Igaku Zasshi 1980; 71 (2):61–83.

Kasahara K Tsuchiya Y Sawato S . Clinical effect of CRD-401 on angina pectoris—an evaluation by double-blind technique. Diagn Treat 1975; 63: 696.

Mizuno Y Yasui S Tobata I . Effect of CRD-401 on ischemic heart diseases. Jpn J Clin Exp Med 1973; 50: 565.

Strauss WE McIntyre KM Parisi AF . Short and long-term efficacy and safety of diltiazem HCl in treatment of propranolol resistant stable angina. Clin Res 1981; 29: 244.

Pepine CJ Feldman RL Whittle J . Effect of diltiazem in patients with variant angina: A randomized double-blind trial. Am Heart J 1981; 101: 719–25.

Rosenthal SJ Ginsburg R Lamb IH . Efficacy of diltiazem for control of symptoms of coronary arterial spasm. Am J Cardiol 1980; 46: 1027–32.

Schroeder JS Feldman RL Giles TD . Multiclinic controlled trial of diltiazem for Prinzmetal's angina. Am J Med 1982: in press.

Yasue H . Effects of diltiazem on angina pectoris in comparison with other antianginal drugs. In: Bing RJ , New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium '78 (No. 487). Amsterdam: Elsevier North Holland, 1979: 219–27.

Kimura E Kishida H . Treatment of variant angina with drugs: A survey of 11 cardiology institutes in Japan. Circulation 1981; 63: 844–8.

Yasue H . Pathophysiology and treatment of coronary arterial spasm. Chest 1980; 78 (July suppl): 216–23.

Yasue H Omote S Matsushita N . Response of angina at rest to various drugs. Jpn Circ J 1976; 40: 472.

Yasue H Omote S Nagao M . Angina decubitus: Responses of angina at rest to various drugs. Mod Med 1976; 31: 2201.

Yasue H Omote S Takizawa A . Pathogenesis and treatment of angina pectoris at rest as seen from its response to various drugs. Jpn Circ J 1978; 42: 1–10.

Yasue H Omote S Takizawa A . Exertional angina pectoris caused by coronary arterial spasm: Effects of various drugs. Am J Cardiol 1979; 43: 647–52.

Yasue H Omote S Takizawa A . Circadian variation of exercise capacity in patients with Prinzmetal's variant angina: Role of exercise-induced coronary arterial spasm. Circulation 1979; 59: 938–48.

Waters DD Theroux P Szlachcic J . Provocative testing with ergonovine to assess the efficacy of treatment with nifedipine, diltiazem and verapamil in variant angina. Am J Cardiol 1981; 48: 123–30.

Cassagnes J Lamaison D Palcoux MC . Treatment of unstable angina by diltiazem. Therapie 1980; 35: 465–73.

Aoi W Suzuki S Doi Y . Clinical use of diltiazem hydrochloride (Herbesser) in hypertension. Clin Rep 1978; 12: 3589.

Ikeda M . Double-blind studies on diltiazem in essential hypertensive patients receiving thiazide therapy. In: Bing RJ , ed. New drug therapy with a calcium antagonist. Diltiazem Hakone Symposium '78 (No. 487). Amsterdam: Elsevier North Holland, 1979: 243–53.

Ikeda M Aoki K Arakawa R . Clinical effect of diltiazem (Herbesser) on essential hypertension; comparison with placebo by double-blind method. Med Progr 1979; 110: 302.

Katsunuma H Koyama T Ishigaki Y . The effect of diltiazem hydrochloride (Herbesser) on hypertension. Med Consult New Remed 1977; 14: 761.

Kawai Y Yamamoto T Ogami T . Clinical effect of diltiazem hydrochloride in hypertension. J Adult Dis 1975; 5: 1495–502.

Kusaba T . The hypotensive effect of Herbesser in essential hypertension. Mod Clin Med 1978; 20: 1859.

Maeda K Takasugi T Tuskano Y . Clinical study of the hypotensive effect of diltiazem hydrochloride. Int J Clin Pharmacol Ther Toxicol 1981; 19: 47–55.

Mue S Takishima T . Clinical use of Herbesser in essential hypertension; special reference to cases complicated with bronchial asthma. Mod Clin Med 1978; 20: 2029.

Ohta T . Long-term observation on clinical hypotensive effect of diltiazem hydrochloride. Clin Rep 1978; 12: 2833.

Sakai K . Long-term Herbesser therapy in hypertension. Mod Clin Med 1978; 20: 1053.

Takahara M . Hypotensive effect of diltiazem hydrochloride on essential hypertension. Clin Rep 1978; 12: 1993.

Tojo S Shishido H Yamamoto S . Effects of CRD-401 on blood pressure and renal function. Jpn J Clin Exp Med 1972; 49: 1958.

Yorifuji S Kawai Y Arami S . Hypotensive effect of diltiazem hydrochloride (Herbesser tablets) in patients with essential hypertension. J Adult Dis 1979; 9: 893–907.

Ikeda M Ogino K Kaneko Y . Clinical effect of diltiazem on essential hypertension. Comparison with propranolol in thiazide combination therapy by double-blind group comparison test. Clin Rep: In press.

Vouhe PR Helias J Grondin CM . Myocardial protection through cold cardioplegia using diltiazem, a calcium channel blocker. Ann Thorac Surg 1980; 30: 342–8.