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Isaac Kobrin - One of the best experts on this subject based on the ideXlab platform.

  • mibefradil a novel Calcium Antagonist in elderly patients with hypertension favorable hemodynamics and pharmacokinetics
    American Heart Journal, 1997
    Co-Authors: Michael Bursztyn, Honer Kadr, Reijo S Tilvis, Benedict Martina, W Oigman, Jonas Talberg, Isaac Kobrin
    Abstract:

    Abstract A multicenter, double-blind, placebo-controlled study of 310 elderly patients with mild-to-moderate essential hypertension was conducted in 20 sites throughout Europe, Brazil, and Israel to assess the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel Calcium Antagonist mibefradil in the elderly. Patients were randomly assigned to receive once-daily doses of 6.25, 12.5, 25, 50, or 100 mg of mibefradil or placebo for 4 weeks. Statistically significant and clinically relevant reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) were observed with the 50 and 100 mg doses. Therapeutic responses reached 88.5% for SDBP and 76.5% for SSBP in the 100 mg group. Trough/peak ratios were >75% in SDBP and SSBP with the 50 mg and 100 mg doses. At doses of 50 to 100 mg once daily, mibefradil was well tolerated and effective with a high antihypertensive response rate and consistent 24-hour blood pressure control in elderly patients. (Am Heart J 1997;134:238-47.)

  • dose response characteristics of mibefradil a novel Calcium Antagonist in the treatment of essential hypertension
    American Journal of Hypertension, 1997
    Co-Authors: Suzanne Oparil, Isaac Kobrin, Darrell R Abernethy, Barton S Levine, Max C Reif, Alexander M M Shepherd
    Abstract:

    The aim of this study was to determine the dose-response characteristics of the Calcium Antagonist, mibefradil, and to evaluate its antihypertensive efficacy and safety in varying doses in patients with mild-to-moderate hypertension. Three hundred and three eligible patients were randomized to receive once-daily 6.25-, 12.5-, 25-, 50-, 100-, 150-, or 200-mg mibefradil doses or placebo for 4 weeks. Repeated blood pressure measurements and electrocardiographic recordings were obtained for the 24 h following the last dose of the placebo run-in period and for the first and last doses of randomized treatment. A statistically significant (P 85% for the 50- and 100-mg doses and 68% and 69% for the 150- and 200-mg doses, respectively. The full antihypertensive effect of mibefradil was achieved within 1 week of treatment. Reductions in sitting systolic blood pressure (SSBP) closely paralleled those in SDBP. The antihypertensive effect of mibefradil was associated with a slight dose-dependent decrease in heart rate and increase in the pulse rate (PR) interval. The appropriate therapeutic dose range of mibefradil in the management of mild-to-moderate essential hypertension is 50 to 100 mg.

  • antihypertensive properties of the novel Calcium Antagonist mibefradil ro 40 5967 a new generation of Calcium Antagonists
    Hypertension, 1996
    Co-Authors: Peter J L M Bernink, Gerold Prager, Arie Schelling, Isaac Kobrin
    Abstract:

    Abstract Preclinical and initial clinical studies suggest that the novel Calcium Antagonist mibefradil has a unique combination of properties. Mibefradil was evaluated in a multicenter, double-blind, placebo-controlled, parallel group trial. After 4 weeks of a placebo run-in period, 202 eligible patients with mild to moderate hypertension were randomized to receive doses of 25, 50, 100, or 150 mg mibefradil or placebo once a day for 4 weeks. Blood pressure and heart rate were measured repeatedly at trough and peak (24 and 2 to 6 hours postdose, respectively) at the end of each period. Concentration-effect relationships were evaluated at trough on the last treatment day. A significant ( P P

  • Effects of the new Calcium Antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: A multicenter, placebo-controlled study
    American heart journal, 1995
    Co-Authors: Ad L.m. Bakx, Ernst E. Van Der Wall, Shimon Braun, Håkan Emanuelsson, Albert V.g. Bruschke, Isaac Kobrin
    Abstract:

    Abstract Mibefradil (Ro 40-5967) is a novel Calcium Antagonist from a new chemical class and is the first that selectively blocks the T-type Calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations >300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type Calcium-channel selectivity.

Barry M Massie - One of the best experts on this subject based on the ideXlab platform.

  • mibefradil a t type channel selective Calcium Antagonist clinical trials in chronic stable angina pectoris
    American Journal of Hypertension, 1998
    Co-Authors: Barry M Massie
    Abstract:

    Pharmacotherapy with nitrates, β-blockers, and Calcium Antagonists is the cornerstone of management of patients with chronic stable angina pectoris. While these agents are all effective, their use may be limited by pharmacologic tolerance, side effects, and drug interactions. Mibefradil is a recently developed Calcium Antagonist with a unique chemical structure, pharmacologic profile, and mode of action. Unlike all previously available Calcium Antagonists, mibefradil acts primarily by selective blockade of T-type Calcium channels, rather than L-type channels, at clinically relevant concentrations. It has been evaluated as a treatment for angina in placebo-controlled and active-controlled clinical trials. Treatment with 50 mg mibefradil resulted in a significant improvement in exercise tolerance test duration in three of the five placebo-controlled trials, and a significant improvement in time to onset of angina in two of the five trials. Time to onset of ischemia as evaluated by 0.1 mV ST-segment depression was increased in all five placebo-controlled trials. Treatment with 100 mg mibefradil resulted in significant improvement in all three exercise tolerance test parameters in all studies. Mibefradil further improved exercise tolerance test duration and other efficacy parameters when administered concomitantly to patients on background β-blocker or nitrate therapy. In addition, treatment with mibefradil was associated with a dose-dependent decrease in heart rate, double product, frequency of anginal attacks, nitroglycerin consumption, and both frequency and duration of silent ischemic episodes. In comparative trials, 100 mg mibefradil once daily was superior in efficacy to 10 mg amlodipine once daily and was at least equivalent to diltiazem in both efficacy and tolerability. Mibefradil was safe and well tolerated in all studies.

  • mibefradil a selective t type Calcium Antagonist
    American Journal of Cardiology, 1997
    Co-Authors: Barry M Massie
    Abstract:

    Mibefradil is the first of a new class of Calcium Antagonists with a unique structure and pharmacology. Its novel mechanism of action is characterized by L-type and selective T-type Calcium channel blockade. Mibefradil is selective for smooth muscle over cardiac muscle and selectively dilates the coronary vasculature over the peripheral vasculature. In animal studies, mibefradil increases coronary blood flow during induced ischemia. In addition, in vitro studies demonstrated that mibefradil decreases smooth muscle proliferation in response to vascular injury. The most intriguing effects of mibefradil include a lack of negative inotropy and reflex tachycardia, as well as inhibition of pathologic hypertrophy and remodeling in response to vascular injury. In clinical trials, mibefradil (100 mg) was more effective than diltiazem dual-release capsules (360 mg) and as effective as amlodipine (10 mg) in treating mild-to-moderate hypertension; mibefradil (100 mg) also resulted in a greater reduction in sitting diastolic blood pressure than did nifedipine GITS (60 mg) in patients with moderate-to-severe hypertension. In patients with chronic stable angina, mibefradil (100 mg) was as effective as diltiazem SR capsules (120 mg) twice daily and more effective than amlodipine (10 mg) in improving exercise tolerance and reducing ischemic episodes. Mibefradil improved survival in a rat model of heart failure as effectively as the angiotensin-converting enzyme (ACE) inhibitor, cilazapril. The apparent lack of negative inotropic activity and neurohormonal activity with mibefradil, as well as its favorable effects on cardiac remodeling in experimental models, suggest that this agent may be beneficial in congestive heart failure. This hypothesis is being tested in the ongoing Mortality Assessment in Congestive Heart Failure (MACH-1) trial.

Ad L.m. Bakx - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the new Calcium Antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: A multicenter, placebo-controlled study
    American heart journal, 1995
    Co-Authors: Ad L.m. Bakx, Ernst E. Van Der Wall, Shimon Braun, Håkan Emanuelsson, Albert V.g. Bruschke, Isaac Kobrin
    Abstract:

    Abstract Mibefradil (Ro 40-5967) is a novel Calcium Antagonist from a new chemical class and is the first that selectively blocks the T-type Calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations >300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type Calcium-channel selectivity.

Georg Noll - One of the best experts on this subject based on the ideXlab platform.

  • pharmacology of the Calcium Antagonist mibefradil
    Journal of Hypertension, 1997
    Co-Authors: Thomas F Luscher, Jeanpaul Clozel, Georg Noll
    Abstract:

    Calcium AntagonistsCalcium Antagonists are potent vasodilators and are widely used in the treatment of hypertension and angina pectoris. The currently available compounds belong to three classes: (1) dihydropyridines (e.g. nifedipine, amlodipine, felodipine), (2) phenylalkylamines (e.g. verapamil) a

Albert V.g. Bruschke - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the new Calcium Antagonist mibefradil (Ro 40-5967) on exercise duration in patients with chronic stable angina pectoris: A multicenter, placebo-controlled study
    American heart journal, 1995
    Co-Authors: Ad L.m. Bakx, Ernst E. Van Der Wall, Shimon Braun, Håkan Emanuelsson, Albert V.g. Bruschke, Isaac Kobrin
    Abstract:

    Abstract Mibefradil (Ro 40-5967) is a novel Calcium Antagonist from a new chemical class and is the first that selectively blocks the T-type Calcium channel. In this multicenter, double-blind, placebo-controlled, parallel designed study, its antianginal and antiischemic effects were evaluated in 126 patients with chronic stable angina pectoris. Exercise tests were performed after 1 week of placebo (baseline) and 2 weeks after randomization to 25, 50, 100, and 150 mg (once daily) or placebo. Highly significant dose-response relations were present across all treatment groups for exercise duration, time to angina, and time to ST-segment depression. They were associated with a dose-dependent decrease in heart rate and blood pressure and plasma concentrations >300 ng/ml. Mibefradil was well tolerated. First-degree atrioventricular block (8%) and dizziness (7%) were the most frequently reported adverse events; however, the first-degree atrioventricular block was dose-related, and only one patient discontinued the trial because of dizziness. The excellent efficacy and adequate safety profile of mibefradil may be a consequence of T-type Calcium-channel selectivity.