Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and safety of once-daily doses of 200, 300, and 400 mg of bepridil hydrochloride were compared with placebo in a 14-week multi-center, double-blind parallel study. All doses of bepridil significantly reduced weekly anginal attacks and nitroglycerin consumption from baseline levels. Bepridil also significantly improved total exercise time, time to angina, time to 1 mm ST-segment depression, and total work. Reduction in heart rate (maximum mean decreases of 7-8 beats/min) and prolongation of QT and corrected QT (QTc) intervals were associated with bepridil therapy. Bepridil was well tolerated; most adverse reactions reported were mild and tolerable even at the 400-mg dose. This study provides strong support for the use of bepridil in patients with chronic stable angina pectoris that is not optimally controlled by other available antianginal therapies. A double-blind withdrawal study is also reported, in which patients stabilized on bepridil were randomized to either continue on bepridil therapy or receive placebo. Patients who were withdrawn from bepridil therapy showed significant increases in the number of weekly anginal attacks and nitroglycerin consumption compared with levels seen during long-term treatment. Patients withdrawn from bepridil therapy showed significant deterioration in exercise tolerance compared with baseline and with those maintained on bepridil.
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PMID:Comparative efficacy of bepridil versus placebo in angina pectoris: treatment and withdrawal studies. 155 91

The efficacy and safety of bepridil hydrochloride (HCl) and propranolol HCl monotherapy were investigated in a double-blind, parallel-group crossover study in 75 patients with chronic stable angina pectoris. For the first double-blind segment, both drugs reduced the frequency of weekly anginal attacks and nitroglycerin consumption. On exercise testing, bepridil was significantly more effective in terms of increasing time to angina and total work. Heart rate and ST-segment depression decreased to a greater degree with propranolol than bepridil. Bepridil produced a greater increase in QT interval than propranolol; corrected QT (QTc) interval was increased by bepridil and slightly decreased by propranolol. The incidence of adverse effects was roughly comparable for the two active drugs and higher than that for placebo during washout periods. It was concluded that bepridil, at a mean maintenance dosage of 324 mg/day, was at least as effective as propranolol in improving exercise tolerance--specifically time to angina and total work--and that tolerability of the 2 drugs was comparable. In another study, the efficacy and safety of bepridil combined with propranolol were compared with that of placebo plus propranolol in 56 patients who had not been well controlled on propranolol alone. The addition of bepridil significantly reduced the frequency of anginal attacks and weekly nitroglycerin consumption compared with baseline. The combination of propranolol and bepridil also produced significant improvements in total exercise time, time to angina, and total work compared with baseline. The QTc interval increased significantly from baseline in the bepridil combination group and decreased significantly in the propranolol plus placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative efficacy and concomitant use of bepridil and beta blockers in the management of angina pectoris. 155 92

The efficacy and safety of bepridil hydrochloride (200 to 400 mg/day) were evaluated in patients with chronic stable angina refractory to maximal tolerated doses of diltiazem (median 360 mg/day) in a randomized, multicenter, double-blind, parallel study. Baseline diltiazem data were obtained during a 2-week period, after which 86 patients were randomized to bepridil (n = 46) or diltiazem (n = 40). Angina frequency, nitroglycerin consumption and ischemic manifestations induced by exercise treadmill testing were evaluated over 8 weeks. Bepridil significantly (p less than 0.05) increased time to angina onset, time to 1 and 2 mm of ST-segment depression, total exercise time and total work over baseline values. Changes in time to angina onset and time to 1 mm of ST-segment depression were significantly (p less than 0.05) greater for bepridil than for diltiazem. Angina frequency and nitroglycerin consumption did not differ significantly between groups. Compared with baseline, bepridil significantly (p less than 0.001) decreased heart rate (mean 4 beats/min) and prolonged QTc (mean 35 ms). The most frequent adverse effects in both groups were nausea, asthenia, dizziness, headache and diarrhea. Four patients taking bepridil and 1 taking diltiazem withdrew from the study because of adverse reactions. No sudden deaths, myocardial infarctions or instances of sustained ventricular tachycardia or torsades de pointes occurred in either group. The data indicate that bepridil provided safe and effective antianginal and antiischemic therapy in patients with chronic stable angina who exhibited less than optimal response to maximal tolerated doses of diltiazem.
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PMID:Comparative efficacy and safety of bepridil and diltiazem in chronic stable angina pectoris refractory to diltiazem. The Bepridil Collaborative Study Group. 185 72

Effects of bepridil, an antiarrhythmic and antianginal drug, on intraventricular conduction in acutely ischaemic and infarcted myocardium were examined in anaesthetized dogs, and compared with those of lidocaine. Bepridil at doses of 2 and 5 mg/kg markedly prolonged the conduction time of a premature excitation induced by a ventricular stimulation in the infarcted zone. The effect of bepridil was dependent on a coupling time of the stimulation. Bepridil showed a marked effect at a coupling time of 150 ms, while it showed no significant effect at a prolonged coupling time of 1 s. In other words, the effect of bepridil was interval-dependent. Lidocaine showed a similar interval-dependent effect, but the effect of lidocaine at a longer coupling time was less than that of bepridil. The premature stimulation produced severely delayed conduction which resulted in reentrant beats. Bepridil blocked these conductions, thereby preventing reentrant beats. In contrast to the depressant effect of bepridil in the infarcted myocardium, bepridil prevented the prolongation of conduction time during acute ischaemia. The alternation of the ST-T complex during acute ischaemia which is also an important arrhythmogenic factor was also attenuated by bepridil. Contrary to bepridil, lidocaine significantly enhanced the conduction delay and the alternation in the ST-T complex. In conclusion, bepridil as well as lidocaine showed an interval-dependent depression of the conduction in the infarcted zone of the heart, whereas during acute ischaemia bepridil in contrast to lidocaine attenuated the conduction delay and ST-T alternans.
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PMID:Effects of bepridil and lidocaine on the intraventricular conduction in acutely ischaemic and infarcted canine myocardium. 209

Rodent muscles were exposed to several organic calcium antagonists, and mechanical responses to direct electrical stimulation were recorded. Verapamil and D600, at 25 microM, depressed twitch and tetanus tension and caused fading of the tetanus plateau. These effects increased with frequency of stimulation, and were not reversed by doubled extracellular calcium. Depression of tension progressed to complete paralysis after 60-90 min exposure to verapamil. Bepridil and diltiazem both caused depression of tension and tetanus fade. Nifedipine caused marked, and nitrendipine caused slight, potentiation of twitch tension but did not alter tetanic tension. The magnitude of the observed effects on tension (either depression or potentiation) correlated with neither the relative calcium antagonist potencies of the drugs in other tissues nor with the ability of the drugs to cross the cell membrane. The continued decline in tension observed on prolonged exposure indicates that chronic exposure to low levels in vivo might lead to significant muscle weakness.
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PMID:Effects of calcium antagonists on mechanical responses of mammalian skeletal muscles. 241 76

The acute hemodynamic and antiischemic effects of intravenous bepridil (3 mg/kg/5 minutes followed by 1 mg/kg/hour) were studied in 19 patients with coronary artery disease under basal conditions and during 2 identical pacing stress tests 30 minutes before (pace test I) and 15 minutes after (pace test II) onset of infusion. Bepridil immediately decreased coronary and systemic vascular resistance (26 and 17%, respectively). This resulted in a 19 and 21% reduction in left ventricular systolic and mean aortic pressures and a 15% increase in coronary flow and stroke index (p less than 0.05 vs control for each). These vasodilating effects were short lasting, persisting for 5 minutes after the bolus infusion, followed by significant reductions in heart rate (15%) and contractility (10%) and a temporary 46% increase in left ventricular filling pressure. During both pace tests heart rate, contractility, coronary flow and myocardial O2 consumption were comparable. In contrast, bepridil prevented the significant increase in systemic resistance and mean aortic pressure observed during pace test I (11 and 15%, respectively). Subsequently, myocardial O2 demand was significantly less during pacing after bepridil, due to an 11% reduction in left ventricular systolic pressure (p less than 0.05 vs control and pacing test II vs I). This resulted in marked antiischemic effects: normalization of lactate extraction and reduction in ST-segment depression (-14 +/- 7 vs 3 +/- 6% and 0.2 +/- 0.02 vs 0.13 +/- 0.02 mV, respectively, pace test I vs II, p less than 0.05), and in less or no angina in 18 patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute hemodynamic and antiischemic properties of intravenous bepridil in coronary artery disease. 278 81

Effects of bepridil [1-[3-isobutoxy-2]benzylphenyl-amino)propyl pyrrolidine) on oxidative phosphorylation, oligomycin-sensitive adenosine triphosphatase, swelling, Ca++ uptake and Na+-induced Ca++ release processes of mitochondria isolated from rabbit heart were investigated. Bepridil, in concentrations greater than 5 microM, produced uncoupling of oxidative phosphorylation and stimulated oligomycin-sensitive adenosine triphosphatase activity. At low concentrations it prevented inorganic phosphate-induced swelling and associated depression of oxidative phosphorylation. Its effectiveness in preventing swelling and depression of oxidative phosphorylation was found to be dependent on inorganic phosphate concentration. A concentration of 1 microM of bepridil was effective in producing 50% less depression of phosphorylating respiration in the presence of 10 mM inorganic phosphate. Concentrations of bepridil above 25 microM inhibited the rate of Ca++ uptake. A 50% inhibition of Ca++ uptake was observed at 93 microM bepridil. The rate of Na+-induced Ca++ release was also inhibited by bepridil. A 50% inhibition of the rate of Na+-induced Ca++ release occurred at 11 microM of bepridil. When the Na+-dependent Ca++ release process was about 80% inhibited by 25 microM bepridil, the uptake process still remained at the same level as the untreated control. Results suggest that in addition to reported effects on sarcolemma and sarcoplasmic reticulum, mitochondria are also affected by bepridil.
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PMID:Action of bepridil, a new calcium channel blocker on oxidative phosphorylation, oligomycin-sensitive adenosine triphosphatase activity, swelling, Ca++ uptake and Na+-induced Ca++ release processes of rabbit heart mitochondria in vitro. 315 32

In the retrogradely perfused, paced rat heart, we studied the effects of the stereoisomers of verapamil (VER), gallopamil (GAL), devapamil (DEV) and bepridil (BEP) on the coronary flow and the maximum systolic left ventricular pressure (MSLVP). In addition, the time courses of onset and recovery of these effects were measured. The verapamil analogues showed high stereoselectivity factors (sf) for MSLVP depression in favour of the (-)-enantiomers and low sf's for coronary flow increase. Bepridil showed a low sf for both parameters with the (+)-enantiomer being more potent. In a previous study we found that in the rat heart, dihydropyridine calcium antagonists clearly possess high selectivity for the vascular isochannel site as compared to the myocardial site, whereas racemic verapamil derivatives were devoid of such selectivity. In the present study the (+)-enantiomers of all verapamil congeners revealed a marked vasoselectivity. This was not found for the (-)-isomers, which surprisingly were virtually equipotent for MSLV depression and coronary flow increase, suggesting a different voltage dependence of the two isochannel verapamil sites for the enantiomers of verapamil and its congeners. Onset and offset velocities were clearly different as well. The kinetics of coronary flow increase were identical and fast for all enantiomers studied. MSLV kinetics were slower. In particular the recovery was markedly different for the enantiomers of each drug, the more potent isomer having the lower velocity. Furthermore, the differences in recovery of MSLVP depression between the verapamil type enantiomers suggest that the recovery rate may directly reflect dissociation from the myocardial isochannel verapamil site.
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PMID:Stereoisomers of calcium antagonists discriminate between coronary vascular and myocardial sites. 325 92

Effect of 1-[3-isobutoxy-2-(benzylphenyl) amino]propyl pyrrolidine hydrochloride (bepridil), a new antianginal agent, on membrane potentials and membrane currents of sinoatrial node cells of rabbits was examined using conventional microelectrode and double microelectrode voltage clamp methods. Bepridil at a concentration of 10 mumol/l caused an increase in spontaneous cycle length, and a decrease in maximum rate of rise of the action potential and action potential amplitude. The rate of diastolic depolarization (phase 4) was also decreased by the drug. In the voltage clamp experiment, bepridil reduced both the slow inward current (Isi) and the hyperpolarization activated current (Ih), and increased the recovery time constant of Isi, whereas the time-dependent potassium current (IK) was not altered significantly. The major effect, however, was the reduction of Isi. These electrophysiological findings suggest that bepridil has a depressant effect on the electrical activity of sinoatrial node mainly by mediating the depression of slow channel.
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PMID:Effect of bepridil on membrane currents of rabbit sinoatrial node cells. 349 89

The electrophysiologic properties of bepridil, a calcium channel blocker with additional effects on fast response tissues, were investigated in 10 patients with atrioventricular accessory pathways. Seven patients had Wolff-Parkinson-White syndrome, and three had concealed atrioventricular pre-excitation. A dose of 4 mg/kg was administered intravenously over five minutes. Bepridil increased the AH interval and the functional refractory period of the atrioventricular node. The effective refractory periods of the right atrium and right ventricle were also increased. Bepridil prolonged refractoriness in the accessory pathway both in the anterograde and retrograde direction. After bepridil administration it was impossible to induce reciprocating tachycardia electrically in two patients because of conduction block in the normal pathway. On the other hand, the zone of tachycardia was often increased after bepridil. Nevertheless, the heart rate during tachycardia was slowed by depression of conduction in both the normal and accessory pathways. The findings of this study provide a basis for the antiarrhythmic action of bepridil in patients with atrioventricular accessory pathways.
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PMID:Electrophysiological action of bepridil on atrioventricular accessory pathways. 349 24


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