Disease relevance of DynaCirc

• CONCLUSIONS: Intravenous isradipine was effective and well tolerated in patients with hypertension after CABG and offers an additional therapeutic option to treat patients after cardiac surgery [1].
• Safety and efficacy of isradipine, alone and in combination, in the treatment of angina pectoris [2].
• However, wedge pressure was maintained with isradipine and there was no tachycardia [3].
• Hemodynamic study of short- and long-term isradipine treatment in patients with chronic ischemic congestive heart failure [4].
• In a double-blind 12-week trial, body weight decreased during isradipine treatment (71.6 to 68.9 kg; p less than 0.01), but there were no significant changes in exercise duration, radionuclide ejection fraction, or cardiothoracic ratio, and no serious side effects were encountered [4].

Psychiatry related information on DynaCirc

• In an acute experiment, isradipine failed to affect locomotor activity on its own either in the place preference boxes or in the open field [5].
• Soon thereafter, he developed acute and severe lethargy, ataxia, dysarthria, and weakness that resolved once isradipine was withheld [6].
• Patient compliance was similar between placebo and isradipine RF and MR treatment [7].
• Absorption from the dose given by gavage was rapid but when administered in a drug diet mixture, isradipine appeared in the plasma slowly and in a manner reflecting the feeding pattern [8].
• The effect of isradipine on maximal electroshock seizures in mice [9].

High impact information on DynaCirc

• OBJECTIVE: To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide [10].
• This heterogeneity in response of presynaptic boutons was not seen with isradipine (5 microM) or omega-agatoxin IVA (80 nM), which inhibited exocytosis by 23% and 17%, respectively [11].
• Only one type, the family of L-type Ca2+ channels (L channels), contains high-affinity binding domains within their alpha 1-subunits for different chemical classes of drugs (Ca2+ channel antagonists; exemplified by isradipine, verapamil and diltiazem) [12].
• Treatment of postoperative hypertension after coronary artery bypass surgery. Double-blind comparison of intravenous isradipine and sodium nitroprusside [1].
• Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall [13].

Chemical compound and disease context of DynaCirc

• The antihypertensive, humoral, and renal effects of acute single oral administration of placebo and isradipine, a new dihydropyridine calcium antagonist, at doses of 2.5 mg, 5.0 mg, and 7.5 mg once daily were investigated in 11 patients with mild-to-moderate uncomplicated essential hypertension [14].
• METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45) [15].
• The effects of combined treatment with the calcium antagonist isradipine and the angiotensin-converting enzyme inhibitor captopril were investigated in a randomized, placebo-controlled parallel-group trial comprising 28 patients with essential hypertension [16].
• Overall, isradipine was found to reduce significantly the angina attack rate and nitroglycerin consumption in patients with chronic, stable, effort-induced angina pectoris [2].
• However, proteinuria in the isradipine group increased by approximately 50% (2.01 +/- 0.40 versus 3.04 +/- 0.70 mg/mg creatinine at baseline versus 6 months, respectively, P < 0.05), whereas captopril reduced proteinuria by 30% after 6 months (2.85 +/- 0.70 at baseline versus 2.30 +/- 0.70 mg/mg creatinine, P < 0.05) [17].

Biological context of DynaCirc

• However, Ang II-induced AA constriction was more sensitive to isradipine than ET-induced constriction (half-maximal inhibitory concentration [IC50], 1.2 +/- 0.2 nmol/L [n = 12] versus 170 +/- 65 nmol/L [n = 19]; P < .01) [18].
• The action of glucagon was mimicked by 8-bromo-cAMP and was blocked by isradipine, suggesting that it relied on the activation of L-type Ca2+ channels, via phosphorylation [19].
• At this dose given daily, PN 200-110 reduced lesion cross-sectional area by 44%, compared with only 25% seen by PY 108-068, which suggests that the antiatherosclerotic effect may not be related to lowering of blood pressure [20].
• Steady state Ca2+ influx at resting potentials (-60 to -40 mV) was voltage-gated and sensitive to the dihydropyridine antagonist PN 200-110 [21].
• Increases in heart rate were mild and similar with all isradipine doses [14].

Anatomical context of DynaCirc

• The thrombin-induced contraction of portal vein strips was completely inhibited by isradipine, and thrombin did not produce an increase in cytosolic [Ca2+], measured by indo-1 fluorescence in cells clamped at -50 mV, sufficient to activate Ca(2+)-dependent chloride current.(ABSTRACT TRUNCATED AT 250 WORDS)[22]
• The observed inhibition by PN 200-110 may relate to mitogen responses of the smooth muscle cell in the vessel wall (migration and proliferation) involved in lesion progression after endothelial damage [20].
• No data are available on the effects of isradipine on a compromised sinus node [23].
• Earlier studies have shown isradipine to reduce the size of infarct in a rat model of embolic stroke (permanent occlusion of the left middle cerebral artery) (Sauter A, Rudin M: Stroke 1986; 17: 1228-1234) [24].
• It is concluded that isradipine in hemodynamically effective doses has no depressant effect on sinus and atrioventricular node function in patients with sick sinus syndrome [23].

Associations of DynaCirc with other chemical compounds

• The binding characteristics of 6 pure stereoisomers, (-) and (+)202-791, (-) and (+)Bay k 8644, (-) and (+)PN 200-110, as well as racemic Bay k 8644 and nitrendipine, were compared [25].
• Palmitate remained stimulatory in islets depolarized with 30 mmol/l extracellular K(+) or exposed to forskolin, but it did not remain stimulatory after treatment with isradipine or triacsin C [26].
• Atenolol had no significant effect on these parameters but, as expected, it lowered the heart rate, which was not affected by isradipine in the long term [27].
• At 6 months, mean arterial pressure was similar (102 +/- 3 and 104 +/- 3 mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged (delta = -4 +/- 3 and +1 +/- 3 ml/min/1.73 in the isradipine and captopril groups, respectively; P = NS) [17].
• Five of 7 patients in the isradipine-treated group and 8 of 9 patients in the propranolol-treated group discontinued the therapy because of adverse reactions or treatment failure [28].

Gene context of DynaCirc

• Here we demonstrate that the four Ca(2+)-channel blockers, Amlodipine, Felodipine, Isradipine and Manidipine, at nanomolar concentrations, activate the transcription of the genes encoding IL-6 and IL-8 in primary human VSMC and fibroblasts [29].
• 2. The results showed that BQ123 and the calcium antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed IMA precontracted with 3 nmol/L ET-1 with the EC50 values of 7.18 +/- 0.09 (-log mol/L) for BQ123, and 7.68 +/- 0.07, 7.02 +/- 0.12, 6.96 +/- 0.08 and 6.89 +/- 0.09 for the calcium antagonists, respectively [30].
• In bFGF-stimulated SMCs, amlodipine and isradipine reduced both Ca2+ influx and ERK 1/2 activation without affecting Ca2+ mobilization [31].
• Reducing BP with isradipine or atenolol results in a similar decrease in platelet activity and PAI-level, tested at rest and 1 h after rest, respectively [32].
• Se-EPO was not changed by the calcium antagonist, isradipine [33].

Analytical, diagnostic and therapeutic context of DynaCirc

• Isradipine reversed AA constriction induced by both peptides [18].
• Furthermore, PN 200-110 did not reduce the extent of platelet deposition (compared with controls) occurring at the denuded vessel surface 1 hour or 24 hours after balloon catheterization, which indicates that the inhibition of lesion development may not reflect an antiplatelet mechanism [20].
• Twenty-three men with essential hypertension participated in a double-blind placebo-controlled study with a crossover design to evaluate the long-term (nine weeks) effects of isradipine on central and renal hemodynamics [34].
• Because of the preference of isradipine for the arterial side of the peripheral vascular tree, the mean peripheral perfusion pressure remained higher in this group than in the atenolol group, although central systemic blood pressure was lowered equally and satisfactorily in both groups [27].
• It is concluded that a slow titration of isradipine by increments at three-week intervals results in an effective and well-tolerated treatment for essential hypertension, both in mono- and combination therapy [35].

References