Disease relevance of Renedil

• Six men with borderline hypertension took felodipine 5 mg with water, grapefruit juice, or orange juice [1].
• Cardiovascular and neurohumoral postural responses and baroreceptor abnormalities during a course of adjunctive vasodilator therapy with felodipine for congestive heart failure [2].
• In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy [3].
• Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial [4].
• The initial tachycardia after felodipine can be diminished by a slow rate of administration of the drug with a similar effect on blood pressure [5].

Psychiatry related information on Renedil

• The effects of various doses (0.03, 0.1, 0.3 or 1.0 mg/kg) of the Ca2+ channel blockers nimodipine, felodipine and amlodipine on the learning ability of rats exposed to electroconvulsive shock were examined [6].
• Felodipine, 5 mg once daily, significantly improved both time to ischemic threshold and pain threshold (p = 0.02 and p = 0.003, respectively, vs placebo), and tended to increase total exercise time (p = 0.06 vs placebo) [7].
• Effects of nimodipine, felodipine and amlodipine on electroconvulsive shock-induced amnesia in the rat [6].
• In a double-blind, placebo-controlled crossover study, the authors evaluated the hormonal and hemodynamic changes during psychological stress and the effect of felodipine 10 mg (plain tablet) [8].

High impact information on Renedil

• Interaction of the antihypertensive drug felodipine with calmodulin [9].
• Before and after receiving grapefruit juice, small bowel and colon mucosal biopsies were obtained endoscopically, oral felodipine kinetics were determined, and liver CYP3A4 activity was measured with the [14C N-methyl] erythromycin breath test in each subject [10].
• Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression [10].
• In addition, enterocyte concentrations of CYP3A4 measured before grapefruit juice consumption correlated with the increase in Cmax when felodipine was taken with either the 1st or the 16th glass of grapefruit juice relative to water (r = 0. 67, P = 0.043, and r = 0.71, P = 0.022, respectively) [10].
• The mean felodipine bioavailability with grapefruit juice was 284 (range 164-469)% of that with water [1].

Chemical compound and disease context of Renedil

• The effects, as monotherapy, of felodipine ER 10 mg o.m. and nifedipine SR 20 mg b.d. were compared in a double-blind, randomized, placebo-controlled, three-way cross-over trial in 43 patients with stable exercise-induced angina pectoris [11].
• The antianginal properties and the duration of action of two doses of felodipine, a dihydropyridine calcium antagonist with a vascular:myocardial potency ratio approximating 100:1, were investigated in 15 patients suffering from disabling effort angina pectoris with reproducible exercise tolerance [12].
• CONCLUSION: Combination of metoprolol and felodipine is to be preferred to felodipine monotherapy in patients who have signs and symptoms of myocardial ischaemia despite optimal beta-blockade [13].
• These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure [14].
• Greater blood pressure reductions by both losartan and felodipine prevented increases in capillarization in skeletal muscle ischemia [15].

Biological context of Renedil

• We conclude that a mechanism for the effect of grapefruit juice on oral felodipine kinetics is its selective downregulation of CYP3A4 in the small intestine [10].
• Felodipine disposition was studied in 10 patients who had microsomal enzyme induction due to chronic anticonvulsant therapy, and in 12 normal volunteers matched for age and sex [16].
• The unloading of cardiopulmonary baroreceptors during upright tilt was substantial and about equal during both treatment courses, but the pulse pressure was maintained during the placebo and decreased during the felodipine period [2].
• At 3 weeks, felodipine reduced the arterial pressure, systemic vascular resistance, and FSVR, preserved cardiac filling pressures and heart rate, and increased cardiac output, stroke volume, and aortic pulsatile stretch [2].
• This study demonstrates that felodipine normalizes baroreflex control of vascular resistance in patients with CHF.(ABSTRACT TRUNCATED AT 250 WORDS)[2]

Anatomical context of Renedil

• In order to study the systemic and coronary haemodynamic effects of felodipine, a new dihydropyridine derivative, 10 patients with coronary artery disease were studied during cardiac catheterization [17].
• Effects on the ischaemic and reperfused myocardium of felodipine, a vasoselective calcium blocker, retrogradely infused into the coronary vein was investigated in a porcine model [18].
• Long-term treatment with the angiotensin I converting enzyme inhibitors during ischemia abolished the increase in the capillary-to-fiber ratio in the soleus muscle, whereas a comparable antihypertensive dose of felodipine had no effect [15].
• These results suggest that felodipine may exert vascular protective effects by suppressing free radical generation in human smooth muscle cells during activation of inflammatory mechanisms and diabetic conditions [19].
• Compared with vehicle alone, felodipine significantly increased NOx generation, Ca2+-dependent NOS activity, and eNOS protein mass in proliferating and quiescent endothelial cells [20].

Associations of Renedil with other chemical compounds

• CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment [3].
• During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life [3].
• Previously we have shown that the fluorescence of the dihydropyridine calcium antagonist felodipine provides an accurate means of monitoring the formation of an allosterically potentiated conformer of calmodulin (Mills, J. S., and Johnson, J. D., (1985) Biochemistry 24, 4897-4903) [21].
• The YFP-based screening allowed the identification of the antihypertensive 1,4-dihydropyridines (DHPs) nifedipine, nicardipine, nimodipine, isradipine, nitrendipine, felodipine, and niguldipine as compounds able to activate deltaF508-CFTR [22].
• The present study compared acute and chronic effects of two classes of calcium channel antagonists, the dihydropyridine type (felodipine) and the phenylalkylamine type (verapamil), on efferent sympathetic outflow and baroreflex slope in 15 essential hypertensive subjects [23].

Gene context of Renedil

• Felodipine tended to increase U-AQP2 [24].
• These findings show that MMP-2 level is raised by treatment with felodipine but not diltiazem, whereas MMP-9 is unaffected by either treatment [25].
• This study was designed to investigate whether treatment with felodipine or diltiazem has any effect on plasma levels of MMP-2 and MMP-9 in essential hypertensive patients [25].
• Each P450 3A preparation catalyzed felodipine oxidation [26].
• Felodipine inhibits nuclear translocation of p42/44 mitogen-activated protein kinase and human smooth muscle cell growth [27].

Analytical, diagnostic and therapeutic context of Renedil

• Cardiomyocytes from four groups of rats were studied: untreated CRF, CRF with parathyroidectomy (PTX), CRF with the calcium channel blocker felodipine (F), and sham operation of the kidney (SO) [28].
• In an open, 3-way, randomized crossover design, 18 healthy volunteers ingested felodipine (10 mg) with 1 of the 3 juices (240 mL) [29].
• Either felodipine (felo-retro group, 7 nmol.kg-1: n = 6) or the corresponding amount of vehicle (vehicle group: n = 5) was retroinfused over 30 min starting 5 min prior to reperfusion [18].
• The ergonovine test was performed once in basal conditions and twice 5 days after beginning the oral administration of felodipine 20 mg o.d., 4 and 24 h after the last administration [30].
• All patients (mean age 79 +/- 6 years, office BP > or = 160/95 mmHg) were evaluated off any antihypertensive or anti-ischaemic therapy and after 3 months treatment with either felodipine or the diuretic (randomized, double-blind study) for episodes of significant ST-D (> or = 0.1 mV, duration > or = 1 min, interval > or = 1 min) [31].

References