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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium antagonists constitute a group of organic compounds with diverse chemical structures. Although their main pharmacodynamic actions are vasodilatation and myocardial depression, they are not uniform in producing these effects. Based on comparison of the potencies in producing negative inotropic, chronotropic and dromotropic effects to the coronary vasodilator potency of individual calcium antagonists determined by use of isolated, blood-perfused papillary muscle, sinoatrial node and atrioventricular node preparations of dogs, calcium antagonists are classified into 2 major groups. The dihydropyridines, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, PN 200-110 (isradipine) and PY 108-068, are generally far more potent in producing coronary vasodilatation than in producing negative inotropic, chronotropic and dromotropic (first-degree atrioventricular block) effects, although there are minor differences among them. The non-dihydropyridine calcium antagonists, verapamil, diltiazem, KB-944, bepridil and MCI-176, are nearly equipotent in producing coronary vasodilatation and a negative dromotropic effect, although all of them are less potent in producing negative inotropy. The non-dihydropyridine calcium antagonists can be further divided into 2 subgroups. Verapamil, diltiazem and KB-944 are nearly equipotent in producing negative dromotropic and chronotropic effects. Bepridil and MCI-176 are less potent in producing negative chronotropy than in producing negative dromotropy.
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PMID:Differences in cardiovascular profile among calcium antagonists. 354 89

The effect of the new vasodilatory and antianginal compound, bepridil (CERM-1978), was examined on the electrical activity of the vascular smooth muscle of isolated dog coronary arteries. Tetraethylammonium (10 mM) was used to induce excitability in the muscle in the form of Ca2+-dependent overshooting action potentials, whose inward current is carried almost exclusively by Ca2+ ion through voltage-dependent slow channels. Bepridil (5 X 10(-7)--1 X 10(--5) M) produced a dose-dependent depression of the rate of rise and amplitude of these Ca2+ spikes. Complete blockade of the action potentials occurred at 1 X 10(-5) M bepridil. These effects of bepridil were antagonized by elevation of external Ca2+ concentration ([CA]o). The effects of bepridil were substantially reversed by washout after about 30 min. Bepridil (10(-5) M) also produced a small but significant (p less than 0.05) increase in resting membrane resistance (input resistance increased from a mean of 10.1 to 12.4 m omega), accompanied by a small but significant (p less than 0.05) depolarization of 6 mV (from a mean of --51 to --45 mV). These latter effects are consistent with a diminution of the resting K+ conductance (gK) by bepridil. It is concluded that the vasodilatory and antianginal properties of bepridil may be explained by the action of this drug in depressing and blocking the Ca2+ influx into the cells, presumably by acting directly on the voltage-dependent slow channels in the cell membrane, and thereby lowering [Ca]i and thus the degree of contraction. Bepridil has Ca2+-antagonistic (or Ca2+ entry blocking or slow channel blocking) properties much like verapamil, but it is somewhat less potent than verapamil in this action (i.e., complete blockade occurred at 10(-5) M bepridil vs. 2 X 10(-6) M verapamil).
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PMID:Bepridil blockade of Ca2+-dependent action potentials in vascular smooth muscle of dog coronary artery. 616 20

Bepridil, a calcium antagonist with a half-life of approximately 42 hours, was compared with placebo in a double-blind, randomized, crossover trial. Thirteen men (average age 62 years) with exercise-related angina pectoris and a positive exercise test (modified Bruce protocol) were studied. In the group as a whole, bepridil (400 mg once a day) caused an increased total exercise time (2.6 +/- 1.8 minutes, mean +/- standard deviation), time to onset of angina (3.3 +/- 1.6 minutes), time to 1 mm of ST-segment depression (2.2 +/- 2.3 minutes), time to 2 mm of ST-segment depression (2.4 +/- 1.4 minutes) and total work load achieved (1.8 +/- 1.4 kpm) compared with the preceding placebo phase (all p less than 0.05). Frequency of angina and nitroglycerin consumption were low and did not change significantly during bepridil therapy. Comparison of the 3 placebo periods (run-in, double-blind and washout) did not reveal a change in any measurement except time to onset of angina, suggesting no training effect or change in patient status. Adverse effects were common in patients taking both placebo and bepridil, but only 2 patients had adverse effects (dizziness) with bepridil that necessitated discontinuation of therapy. Similarity of the double product (systolic blood pressure X heart rate) at the end of exercise suggests a decrease in myocardial oxygen demand as the primary mode of action. This study suggests that bepridil is a promising agent for the treatment of exercise-induced myocardial ischemia.
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PMID:Effects of bepridil on exercise tolerance in chronic stable angina: a double-blind, randomized, placebo-controlled, crossover trial. 636 14

The action of four calcium antagonistic drugs, including verapamil, bepridil, nifedipine, and diltiazem, on calcium binding to cardiac sarcolemma from guniea pig was tested. It was found that verapamil (10(-6) to 10(-5) M) inhibited calcium binding to a great extent. Bepridil at the same concentrations was less potent than verapamil in the depression of calcium binding. Nifedipine and diltiazem did not affect sarcolemmal calcium binding. The differential action of the calcium antagonistic drugs was discussed.
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PMID:Differential actions of calcium antagonists on calcium binding to cardiac sarcolemma. 698 16

Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.
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PMID:Bepridil improves left ventricular performance in patients with angina pectoris. 750 41

Bepridil has been used only rarely in unstable angina since its long half-life could imply a delayed action. A loading dose could deal with this disadvantage. In order to confirm this hypothesis, a randomised trial was undertaken involving a 5 day comparison of bepridil at the dose of 300 mg/day after a loading dose (900 mg on D1, 500 mg on D2 and D3) with diltiazem 360 mg/day in 277 patients: 210 men and 67 women, with a mean age of 62.1 +/- 9.5, suffering from unstable angina confirmed by an ECG during symptomatic events showing reversible ST depression. A continuous 72 hour ECG record was obtained in 82 patients. Because of 69 inclusion errors, only 208 patients provided evaluable data (110 with bepridil and 98 with diltiazem), including 55 with continuous ECGs. Mortality (4.5% bepridil v. 3.1% diltiazem) and premature treatment terminations for therapeutic inefficacy (4.5% bepridil v. 7.1% diltiazem), myocardial infarction (3.6% bepridil v. 3% diltiazem), adverse events (3.6% bepridil v. 3% diltiazem) or at the patient's request (0.9% bepridil) were similar between the 2 groups. Efficacy regarding angina was similar, with 18.2% recurrences with bepridil and 21.4% with diltiazem during the first 72 hours, persisting without any difference beyond 72 hours. Resulting treatment adjustments concerning nitrates were identical in the 2 groups. Among the 55 patients with an evaluable continuous ECG (27 bepridil and 28 diltiazem, NS), 18 had recurrent ischemic episodes (9 bepridil and 9 diltiazem), 72.2% of which were clinically silent. Their total number, total duration and maximum amplitude of ST depression were similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Comparative study of the efficacy and tolerability of bepridil and diltiazem in unstable angina. 277 patients]. 817 82

1. By use of patch-clamp techniques, the effects of SD-3212, a novel antiarrhythmic drug, on the calcium current (Ica), the sodium current (INa) and the muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) were examined and compared with those of bepridil in guinea-pig single atrial cells. 2. SD-3212 inhibited ICa and INa in a concentration-dependent manner. The IC50 values of SD-3212 for inhibition of ICa and INa were 1.29 microM and 3.92 microM, respectively. The steady state inactivation curves of ICa and INa were shifted in the hyperpolarizing direction in the presence of 1 microM SD-3212. Similar inhibition of ICa and INa was also observed with bepridil. The IC50 values of bepridil for depression of ICa and INa were 1.55 microM and 4.43 microM, respectively. 3. The muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) was activated by the extracellular application of 1 microM carbachol in the GTP-loaded cells or by the intracellular loading of GTP gamma S, a nonhydrolysable GTP analogue. SD-3212 potently inhibited the carbachol- and GTP gamma S-induced IK.ACh and the IC50 values were 0.38 microM and 0.20 microM, respectively. These IC50 values were very close and about 10 times lower than those for inhibiting ICa and INa. Bepridil also suppressed the carbachol- and GTP gamma S-induced IK.ACh with the IC50 values of 0.69 microM and 0.84 microM, respectively. 4. In guinea-pig atrial cells stimulated at 0.2 Hz, carbachol at a concentration of 1 microM markedly shortened action potential duration. Both SD-3212 (0.1-1 microM) and bepridil (1-10 microM) reversed the action potential shortening in a concentration-dependent manner. The antagonizing effect of SD-3212 on the carbachol-induced action potential shortening was more potent than that of bepridil. 5. These results suggest that SD-3212 inhibits IK.ACh by depressing the function of the potassium channel itself and/or associated GTP-binding proteins. SD-3212 is a unique antiarrhythmic drug, which potently inhibits IK.Ach in addition to its class I and IV effects. SD-3212 and bepridil may be useful for the termination and prevention of vagally-induced atrial flutter and fibrillation.
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PMID:SD-3212, a new class I and IV antiarrhythmic drug: a potent inhibitor of the muscarinic acetylcholine-receptor-operated potassium current in guinea-pig atrial cells. 859 Oct

Bepridil (Cordium) is a calcium channel blocker which has been demonstrated to be effective in the preventive treatment of angina. Few controlled trials have compared bepridil to diltiazem (Tildiem), the reference calcium channel blocker. The objective of this study was to evaluate the efficacy and safety of bepridil in stable coronary patients. 148 patients (139 M, 9 F, mean age: 58 +/- 8.6 years), with documented coronary artery disease and positive stress test after 5 days of placebo were included. After double-blind randomization, they received bepridil (300 mg/day ion 3 doses), or diltiazem (180 mg+/day in 3 doses) for 15 days. A stress test was then performed under the same conditions as on inclusion. The anti-ischaemic efficacy of the two drugs was comparable. Total work increased from 4,552.4 +/- 2,179.4 Kpm a 6,103.2 +/- 2,849.2 Kpm with bepridil (p < or = 0.0001) and from 4,524.8 +/- 2,160.5 Kpm a 5,848.3 +/- 2,800.3 Kpm (p < or = 0.0001) with diltiazem, with no intergroup difference. Duration of effort was significantly prolonged: from 10.5 +/- 3.0 min to 12.5 +/- 3.3 min with bepridil (p < or = 0.0001) and from 10.5 +/- 2.9 min to 12.1 +/- 3.4 min with diltiazem (p < or = 0.0001), with no intergroup difference. The time to onset of 1 min of ST depression increased significantly between the two stress tests, from 8.36 +/- 2.7 min to 10.82 +/- 3.4 min with bepridil (p < or = 0.001) and from 8.02 +/- 3.0 min to 10.53 +/- 3.6 min with diltiazem (p < or = 0.001), with no significant difference between the two groups. The clinical safety of the two products was comparable. On the electrocardiogram, the QT interval was significantly prolonged with bepridil, from 368.6 +/- 37.5 msec to 393.6 +/- 38.7 msec (p < or = 0.0001), reflecting cellular impregnation of the drug.
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PMID:[Comparison of anti-ischemic effect of bepridil and diltiazem evaluated by exercise test in patients with coronary disease. A multicenter study. Groupe d'Investigateurs]. 953 75

Bepridil is an investigational calcium antagonist that also has fast sodium channel blocking and antidysrhythmic properties. In the present study, the potential interactions of bepridil with volatile anesthetics on cardiac electrophysiologic parameters were evaluated in open-chest dogs. Twenty-four dogs anesthetized with enflurane (n=6), halothane (n=6), isoflurane (n=6), or chloralose (n=6) received 2.5 mg/kg of bepridil intravenously (IV). Twenty-five additional dogs anesthetized with enflurane (n=7), halothane (n=6), isoflurane (n=6), or chloralose (n=6), received bepridil, 5.0 mg/kg, IV. Dogs anesthetized with cloralose served as controls. Cardiac electrophysiologic parameters were measured after the dogs were anesthetized and were repeated 5, 15, 30, 45, and 60 minutes after bepridil infusion. Plasma bepridil concentrations were also determined at the above time points. Synergy between bepridil and enflurane was demonstrated in the following cardiac electrophysiologic parameters: depression of sinus node function as evidenced by severe depression of sinus node automaticity and conduction; depression of atrioventricular function as evidenced by prolongation of the atrial-His bundle interval and the Wenckebach R-R interval; and, prolongation of the atrial effective refractory period. No synergy was demonstrated between bepridil and halothane or isoflurane when compared to bepridil's effects during chloralose anesthesia. It is concluded that significant synergistic cardiac electrophysiologic effects exist between bepridil and enflurane in dogs. It is recommended that caution be used when anesthetizing patients receiving bepridil with enflurane until human data on the use of this combination of pharmacologic agents is available.
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PMID:Cardiac electrophysiologic interactions of bepridil, a new calcium antagonist, with enflurane, halothane, and isoflurane. 1717 71


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