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At least 19 recordsLinked to original sources

PubMed1997

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group.

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. 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). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.

Antihypertensive Agents↗

PubMed1992

Efficacy and tolerability of isradipine and metoprolol in treatment of hypertension: the Finnish Isradipine Study in Hypertension (FISH).

Eight hundred seventy-six men and women with diastolic blood pressure (DBP) of 95-115 mm Hg during a 4-week placebo period were included in a multicenter trial; 479 patients had previously been treated for hypertension. The patients were randomized to receive isradipine or metoprolol; both groups were comparable for age, weight, height, smoking habits, and duration of hypertension. By the end of the placebo period, 79 patients did not fulfill the final entry criteria and were withdrawn. The isradipine group consisted of 398 patients (164 women and 234 men), and the metoprolol group consisted of 399 patients (173 women and 226 men). The initial dose of isradipine was 1.25 mg twice daily (b.i.d.), and the initial dose of metoprolol was 50 mg b.i.d.; the doses were doubled after 4 weeks if DBP had not decreased to less than or equal to 90 mm Hg. After 8 weeks, the isradipine group began combination therapy with metoprolol 50 mg b.i.d. and the metoprolol group began combination therapy with isradipine 1.25 mg b.i.d. if DBP was not less than or equal to 90 mm Hg. After 8 weeks monotherapy, mean BP (MBP) was reduced by 13/11 mm Hg (161/104 to 148/93) in the isradipine group and by 15/12 mm Hg (160/103 to 145/91) in the metoprolol group. Monotherapy with isradipine normalized DBP to less than or equal to 90 mm Hg in 52% with a mean dose of 4.26 mg daily, and monotherapy with metoprolol normalized DBP in 58% with a mean dose of 155 mg daily.1+

Adult↗

PubMed1989

Evaluation of the safety and efficacy of isradipine in elderly patients with essential hypertension. The British Isradipine Hypertension Group.

One hundred eighteen patients, aged between 65 and 87 years with mild-to-moderate hypertension were given placebo or isradipine (1.25 to 5 mg twice daily, or 2.5 to 10 mg once daily) following a three-week placebo period to evaluate its safety and efficacy in elderly patients. Dosage step-up was at three-week intervals. Blood pressure measurements were taken immediately before the morning dose (12 to 24 hours after the previous dose). At the end of the study, both supine and standing diastolic blood pressures were significantly lower with isradipine than with placebo. A 10-mm Hg reduction in supine diastolic blood pressure was achieved with once-daily isradipine in 65 percent and with twice-daily isradipine in 52 percent of patients, indicating sustained blood pressure control over the dose interval (12 to 24 hours). Adverse events were usually mild, transient, and typical for vasodilators. Isradipine did not produce more laboratory, clinical, or electrocardiographic abnormalities than did placebo. In conclusion, isradipine either once or twice daily at doses between 2.5 and 10 mg is an effective and well-tolerated treatment for mild-to-moderate hypertension in elderly patients.

Aged↗

PubMed1993

Isradipine in the treatment of mild-to-moderate hypertension. The Austrian Multicenter Isradipine cum Spirapril Study (AMICUS).

The objective of this study was to assess the safety and efficacy of 1.25 to 2.5 mg of isradipine twice daily in patients with mild-to-moderate hypertension, as seen in general practice. A total of 595 patients were treated for 6 months with an initial dose of isradipine at 1.25 mg twice daily. This dose was doubled if normotension (diastolic blood pressure [DBP] < or = 90 mm Hg) was not achieved after 4 weeks of treatment (n = 327). If, after 8 weeks, blood pressure was still not normalized, either the angiotensin-converting enzyme (ACE) inhibitor spirapril at 3 mg (n = 58) or the beta-blocker pindolol at 5 mg (n = 54) was added to the treatment. After 24 weeks, the mean blood pressure decrease with isradipine at 1.25 mg twice daily was 28.5/19.0 mm Hg for systolic blood pressure (SBP)/DBP and, with 2.5 mg isradipine twice daily, 28.4/18.5 mm Hg. There was no relevant change in heart rate. The overall normalization rate for all 595 patients was 78.2%. Side-effects that were considered related or possibly related to treatment were reported in 73 patients (12.3%). Treatment with isradipine plus either spirapril or pindolol was discontinued in 32 patients (5.4%) because of side-effects related, or possibly related, to the study treatment. Blood pressure was also self-recorded in a subgroup of 45 patients. The self-recorded values were 11/6 mm Hg (SBP/DBP) lower than the respective causal readings at the start of active treatment. However, this difference disappeared completely after 8 weeks of treatment.

Adult↗

PubMedDate not supplied

A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group.

Isradipine is a dihydropyridine calcium-entry blocker. Previous controlled and blinded trials have demonstrated the safety and efficacy of isradipine in lowering blood pressure in patients with hypertension. The purpose of this study was to reassess this safety and efficacy in a large number of patients in an open-label, long-term, multicenter trial. A total of 501 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) received 5 to 10 mg/d of isradipine in two divided doses for a period of 32 weeks. The mean dose used was 7.4 mg/d with titration at week 4 from 5 mg/d (2.5 mg BID) to 10 mg/d (5 mg BID) if the diastolic pressure was still > 90 mm Hg. After 32 weeks of isradipine treatment, systolic blood pressure decreased from 154.9 +/- 16.4 mm Hg to 140.2 +/- 13.9 mm Hg (P < 0.001) and diastolic pressure from 101.2 +/- 5.2 mm Hg to 86.6 +/- 7.9 mm Hg (P < 0.001). This monotherapy was successful in reducing diastolic blood pressure > 10 mm Hg in 62.5% of the patients. Significant adverse effects were noted in 92 (18.4%) of the 501 patients; only 30 (6.0%) withdrew from the study because of adverse events. In this large, long-term, community-based study, isradipine was effective and well tolerated in most patients.

Adult↗

PubMed1989

Multicenter evaluation of the safety and efficacy of isradipine in hypertension. The Italian-Belgian Isradipine Study Group.

One hundred seventy-eight patients, aged 30 to 85, with mild-to-moderate hypertension entered a multicenter double-blind, randomized, between-patient comparison of isradipine (0.5, 1.25, or 2.5 mg twice daily) and placebo. Patients were assessed after three weeks of placebo treatment (for baseline) and after two and five weeks of active therapy. Despite a marked placebo effect, isradipine at 1.25 mg and 2.5 mg twice daily reduced blood pressure to a significantly lower level. The lowest blood pressures were recorded at four hours post-dose, and the residual antihypertensive effect at 12 hours was between 70 and 79 percent of the four-hour measurements. Isradipine did not produce more laboratory, electrocardiographic, or clinical abnormalities, or adverse events than did placebo. It is concluded that isradipine in doses of 1.25 mg and 2.5 mg twice daily is effective and well tolerated in the treatment of mild-to-moderate hypertension.

Adult↗

PubMed1991

A randomized comparison of isradipine slow release given once daily with isradipine twice daily on 24 hour blood pressure in hypertensive patients.

Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.

Adult↗

PubMed1989

A multicenter evaluation of the safety and efficacy of isradipine and atenolol in the treatment of hypertension. Isradipine in Hypertension Study Group.

A total of 152 patients with essential hypertension (World Health Organization classification I/II) entered a multicenter randomized study to assess the safety and efficacy of isradipine compared with, and in combination with, the beta-blocker atenolol. After a three-week placebo treatment period, patients received either isradipine (2.5, 5, 7.5, or 10 mg twice daily) or atenolol (50 or 100 mg once daily) for seven weeks. Patients who did not have an adequate response (diastolic blood pressure less than 90 mm Hg) with the maximal doses of single-drug therapy were given a combination of both drugs for a further seven weeks. Both drugs resulted in significant and clinically relevant reductions in blood pressures. Although the reduction in diastolic blood pressure was the same for patients receiving the two drugs, there was a statistically significant greater reduction in systolic blood pressure in the isradipine group, suggesting that this drug has a more favorable effect on vascular impedance. Of the 14 patients who did not attain normal blood pressure levels (sitting diastolic blood pressure less than 90 mm Hg) receiving monotherapy, 12 patients reached this goal with a combination of the two drugs.

Antihypertensive Agents↗

PubMed1995

Sustained blood pressure control with controlled-release isradipine (isradipine-CR).

The safety and efficacy, as measured by peak/trough blood pressure reduction, of a new, once-daily, controlled-release formulation of isradipine (isradipine-CR, ICR) were evaluated in patients with mild to moderate essential hypertension during a nine-week trial. After a 3-week placebo washout period, patients with a sitting diastolic blood pressure between 100 and 114 mm Hg were randomized to either 1 of 4 ICR treatment groups or placebo. Of 402 randomized patients, 384 completed the study (placebo = 77, ICR-5 mg = 76, ICR 10 mg = 76, ICR-15 mg = 78, and ICR-20 mg = 77). Peak and trough post-dose blood pressure responses and heart rates were monitored for both the sitting and upright positions. Blood chemistries, urinalyses, complete blood counts, and electrocardiograms were done during the study. Both sitting and upright blood pressure decreased with the 5-(P < .05), 10-, 15-, and 20-mg (P < .001) once-daily ICR doses. The peak blood pressure reduction for all ICR doses occurred at 8 to 10 hours post-dose. Maximum peak/trough blood pressure response, achieved with the 10-mg dose, was similar with that of 15 and 20 mg of ICR. No serious clinical or metabolic side effect were noted, except ankle edema, which was dose dependent but did not require discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1997

Isradipine and naltrexone in combination with isradipine interact with a period of abstinence to reduce rats' intakes of an alcoholic beverage.

Individually housed rats were placed on a daily regimen of only 2 hr a day to drink both water and a sweetened alcoholic beverage. Initially, rats took little ethanol, but after 3 weeks, they took, on average, >2.0 g/kg daily. With achievement of stable intakes, the rats were deprived of opportunity to drink ethanol for 24 days and then the daily regimen was reinstated. With the reinstatement, various injections were given daily for 25 days or more: placebos, doses of isradipine (1.0 or 3.0 mg/kg), naltrexone (3.0 mg/kg), and a combination of isradipine (1.0 mg/kg) and naltrexone (3.0 mg/kg). The combination produced favorable effects with the fewest limiting side-effects. The period of abstinence decreased daily intakes of ethanol and interacted with the drugs to produce large, sustained decreases in intakes of ethanol.

Alcohol Drinking↗

PubMed1994

Influence of isradipine treatment on the morphology of the aorta in spontaneously hypertensive rats.

OBJECTIVE: To investigate the influence of hypertension and of treatment with the vasodilator hydralazine or with the dihydropyridine calcium antagonist isradipine on the morphology of the thoracic aorta in spontaneously hypertensive rats (SHR). DESIGN: The systolic blood pressure (SBP), body weight and morphology of the thoracic aorta were evaluated. The ultrastructure of the smooth muscle component of the aorta and of the tunica intima were analysed by transmission and scanning electron microscopy. METHODS: The SHR were divided into three groups: a control group, which was left untreated, and two treatment groups, one with 1 mg/kg per day hydralazine and the other with 0.1 mg/kg per day isradipine. Three age-matched groups of Wistar-Kyoto (WKY) rats were included in the study: one group was left untreated and was used as a normotensive reference group, the other two groups were treated with 1 mg/kg per day hydralazine or with 0.1 mg/kg per day isradipine. RESULTS: The SBP did not change in the WKY rats treated with hydralazine, with isradipine or untreated, but was significantly increased in the SHR as a function of age. Both hydralazine and isradipine significantly reduced the SBP in the SHR after the second week of treatment. Light microscopy analysis of the thoracic aorta revealed thickening of the wall of the tunica media as well as an increase in the wall: lumen ratio in the SHR. Treatment with hydralazine had no effect on the morphometric parameters evaluated, whereas isradipine administration significantly reduced the thickening of both the wall and the tunica media of the aorta, and reduced the wall: lumen ratio. No significant modifications in the structure of the thoracic aorta were noticed in the hydralazine- or isradipine-treated WKY rats compared with untreated WKY rats. Transmission and scanning electron microscopy analysis demonstrated in control SHR hypertrophy of smooth muscle cells of the tunica media, an increased size and impairment of the internal elastic lamina, and a widening of the subendothelial space. Hypertrophy of the endothelium was also noticeable in the SHR. Treatment with isradipine reduced the hypertrophy of smooth muscle cells of the tunica media and the structural impairment of the tunica intima. No effect of isradipine treatment on the morphology of the aorta was noticed in the WKY rats. CONCLUSION: The present results show that the effect of isradipine was different from that of hydralazine. Both compounds lowered the SBP, but only isradipine countered the structural changes of the aorta in the SHR. The effect of isradipine administration is particularly pronounced on the hypertension-dependent changes of endothelium. This suggests that isradipine may have a protective effect on the endothelium.

Animals↗

PubMed1994

Duration of effects of isradipine during twice daily therapy in angina pectoris.

Isradipine, a 1,4 dihydropyridine calcium channel antagonist, is a potent coronary artery dilator that increases coronary blood flow with little effect on cardiac contractility. Isradipine is an approved antihypertensive agent, but its antianginal effects have not been well documented. In this placebo-controlled, double-blind, parallel-group design study we evaluated the duration of effects and safety of isradipine 10 mg bid in male patients with chronic stable angina pectoris. Seventy-two patients experiencing moderately severe angina between 3 and 7.5 minutes during a standard Bruce exercise test received placebo in a single-blind manner for 8-14 days. Sixty-one of these patients had reproducible treadmill exercise test results on three consecutive occasions and underwent further exercise tests at 3, 8, and 12 hours after a placebo period. Patients were then randomized (double blind) to either placebo or isradipine 10 mg bid for 2 weeks. Symptom-limited exercise tests were repeated predose and at 3, 8, and 12 hours after the 0800 hour dose dosing. Exercise duration increased significantly from baseline (last qualifying test during the single-blind placebo therapy, i.e., 0800 hours predose at visit 4) in the isradipine group compared to the placebo group prior to the administration of the 0800 hour dose (i.e., 12 hours after the 2000 hour dose) by 51 vs. 18 seconds, p = 0.04; and after the administration of the 0800 hour dose at 3 hours by 78 vs. 29 seconds, p = 0.005; and at 8 hours by 54 vs. 18 seconds, p = 0.04. Similarly, statistical significance was achieved when exercise data were analyzed using visit 4 (single-blind placebo therapy) corresponding time points as baseline. At 12 hours after the 0800 hour dose, exercise tolerance did not increase significantly after isradipine compared to placebo. Time to 1-mm ST-segment depression increased significantly after isradipine at 3 hours post 0800 hour dose compared to placebo (87 vs. 7 seconds, p < 0.01) but not at the 0, 8, or 12-hour postdose time points, regardless of which baseline was used. Isradipine therapy did not affect the rate-pressure double product. A significant correlation between the mean increase in total exercise time and mean plasma isradipine concentration was also present (p = 0.0295). During double-blind treatment, drug-related adverse events were experienced by four patients in the isradipine group and two patients in the placebo group. None of the patients experienced ischemic complications during the study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1994

Effect of isradipine on the formation and regression of fatty streaks in cholesterol fed rabbits.

OBJECTIVE: The aim was to determine whether the antiatherogenic effect of the calcium channel blocker isradipine on fatty streak formation was dependent upon a temporal relationship between cholesterol feeding and administration of the drug. METHODS: The study was done in New Zealand White rabbits fed a diet supplemented with cholesterol (2.5% w/w) for three weeks. Such a regimen results in loss of endothelium dependent relaxation and accumulation of cholesterol in the aorta four weeks later. The calcium antagonist isradipine was given in a dose of 0.25 mg.kg-1.d-1 at specified periods during the study to seven subgroups of animals: (1) standard diet + 2.5% cholesterol for three weeks; (2) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks; (3) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks; (4) standard diet + 2.5% cholesterol+isradipine for three weeks followed by standard diet alone for four weeks; (5) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given throughout the seven weeks; (6) standard diet + 2.5% cholesterol for three weeks followed by standard diet for four weeks with isradipine given during the final four weeks only; (7) standard diet + 2.5% cholesterol for three weeks followed by standard diet for 12 weeks with isradipine given during the final eight weeks. Aortic tissue was removed for measurement of cholesterol content, endothelium dependent relaxation to acetylcholine and the calcium ionophore A23187, and relaxant responses to sodium nitrite. Serum was collected for measurement of cholesterol and triglyceride concentration. RESULTS: When isradipine was given either during cholesterol feeding and continued for four weeks following it (subgroup 5) or during the four weeks following cholesterol feeding (subgroup 6), loss of endothelium dependent relaxation and the accumulation of cholesterol in the aorta was prevented. However, administration of isradipine during the period of cholesterol feeding alone (subgroup 4) was without effect. Also, administration of isradipine after lesions of fatty acid streak type were established appeared to have a favourable effect on removal of cholesterol from the aorta. CONCLUSIONS: Isradipine protects against the development of fatty streaks in rabbits fed a diet supplemented with 2.5% cholesterol. Administration of this drug after fatty streaks are formed also promotes their resolution.

Acetylcholine↗

PubMed1995

Failure of isradipine to reduce infarct size in mouse, gerbil, and rat models of cerebral ischemia.

BACKGROUND AND PURPOSE: The dihydropyridine L-type calcium channel blocker isradipine has been reported to exhibit neuroprotective properties in some, but not all, studies performed in the rat middle cerebral artery occlusion (MCAO) model. In the present study, we examined isradipine in several other models of focal and global ischemia: rat rose bengal, mouse MCAO, and gerbil bilateral carotid artery occlusion (BCAO). For comparison, a novel calcium channel blocker, SB201823A, that we have previously shown to be neuroprotective in rat and gerbil models was also examined in the mouse. METHODS: In the gerbil BCAO model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10). Corresponding controls received vehicle (n = 10), and sham-operated animals received no treatment (n = 6). Locomotor activity and histological assessments were made at 4 days after ischemia. In the rat photothrombotic occlusion model, isradipine was administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia (n = 10), and corresponding controls (n = 10) received vehicle. Histological assessment was made at 7 days after ischemia. In the mouse MCAO model, isradipine was also administered at 2.5 mg/kg i.p. as a single dose 60 minutes after ischemia. Histological assessments were made at 1 (n = 13), 2 (n = 9), and 4 (n = 9) days after ischemia. Vehicle numbers were n = 10, n = 6, and n = 8, respectively. Isradipine and SB201823A were also examined using a combined preischemia and postischemia regimen. Isradipine was administered at 2.5 mg/kg i.p. before occlusion, 1.25 mg/kg i.p. 1 hour after occlusion, 1.25 mg/kg i.p. 2 hours after occlusion, and 2.5 mg/kg twice a day for 3 days after occlusion (n = 16). Corresponding controls received vehicle at the same time points (n = 14). SB201823A was administered 30 minutes before occlusion, 30 minutes after occlusion, and twice daily for 3 days (n = 12). Corresponding controls received vehicle (n = 9). Histological assessment was performed at 4 days after ischemia. RESULTS: When given after ischemia, isradipine failed to affect lesion volume in both the rat and mouse models. In the gerbil, locomotor hyperactivity and hippocampal cell loss were unaffected. Given before and after ischemia in the mouse, isradipine was also ineffective, whereas SB201823A produced a significant reduction in lesion volume. CONCLUSIONS: The L-type calcium channel blocker isradipine was devoid of neuroprotective activity in focal and global models of cerebral ischemia in three species of normotensive animals. These results were compared with data for the novel calcium channel blocker SB201823A, which exhibited a significant effect after pre- and postocclusion administration in the mouse model of permanent focal ischemia.

Animals↗

PubMed1989

Myocardial properties of the new dihydropyridine calcium antagonist isradipine compared to nifedipine with or without additional beta blockade in coronary artery disease.

Isradipine is a new dihydropyridine calcium antagonist with myocardial effects significantly different from those of nifedipine, as shown by in vitro and animal experimental data. Isradipine selectively inhibits the sinus node but not the atrioventricular conduction and its negative inotropic action is much less if administered in a dose of comparable peripheral effects. To study these effects in man, 40 patients with coronary artery disease were divided into 2 groups receiving either a continuous 30-minute intravenous infusion of 2 mg of nifedipine or 0.5 mg of isradipine, doses that resulted in a comparable afterload reduction (decrease of systemic vascular resistance: nifedipine -22.1%, isradipine -25%, p less than 0.001). Ten patients in each group received an additional intravenous bolus of 5 mg of propranolol at the end of the calcium antagonist administration to antagonize its induced adrenergic reflex mechanisms. The heart rate significantly increased after nifedipine only (+9.2%, p less than 0.001), experienced no change after isradipine and the nifedipine and propranolol combination and decreased after the combination of isradipine and propranolol (-9.6%, p less than 0.001). This resulted in a significant decrease of the rate pressure product with isradipine (-12.5%, p less than 0.001) but not with nifedipine. As a result of the afterload-induced adrenergic reflex mechanisms, the maximal derivative of the left ventricular pressure increased after isradipine administration (+13.5%, p less than 0.001) and was unchanged after nifedipine, which demonstrates the significantly less negative inotropic properties of isradipine as compared with nifedipine.

Adrenergic beta-Antagonists↗

PubMed1993

Radioligand and functional estimates of the interaction of the 1,4-dihydropyridines, isradipine and lacidipine, with calcium channels in smooth muscle.

1. The present experiments were undertaken in order to characterize further the apparently irreversible inhibition of the contraction of depolarized rat aorta caused by lacidipine, a 1,4-dihydropyridine calcium antagonist. 2. We studied the effect of lacidipine on contraction evoked by 100 mM KCl solution in rat aorta, treated by N omega-nitro-L-arginine (0.1 mM), an inhibitor of nitric oxide (NO) synthesis. We compared the effect of prolonged depolarization on lacidipine and (+)-isradipine inhibition and the reversal of this inhibition after washout in the absence of dihydropyridines. Assuming that the onset of lacidipine-evoked inhibition was a pseudo-first order association kinetics, we estimated the dissociation rate constant (k-1 = 0.031 min-1), the association rate constant (k1 = 2.70 x 10(8) M-1 min-1) and the dissociation constant (KD = k-1/k1 = 115 pM) which was close to the IC50 value in steady-state conditions (160 pM). 3. The inhibitory effects of lacidipine and (+)-isradipine on rat aorta contraction were reversibly enhanced after preincubation with the drug in a 40 mM KCl-solution. Washout with drug-free 40 mM K(+)-depolarizing solution reversed inhibition in the (+)-isradipine-treated preparations, but not in the lacidipine-treated ones. 4. Radioligand binding studies were performed with [3H]-lacidipine and [3H]-isradipine in microsomes from rat aorta and rat ileum. Both ligands bound to a homogeneous population of binding sites (for[3H]-lacidipine: KD = 23 +/- 2.6 pM, Bmax = 380 +/- 21 fmol mg-1 protein in membranes from aorta; KD =23 +/- 3.1 pM, Bmax = 790 +/- 60 fmol mg-1 protein in membranes from ileum; for [3H]-isradipine:KD = 140 +/- 46 pM, Bmax = 350 +/- 64 fmol mg-1 protein in membrane from aorta; KD = 68 +/- 14 pM,Bmax = 760 +/- 75 fmol mg-1 protein in membranes from ileum). After isotopic dilution, [3H]-lacidipine and [3H]-isradipine dissociated according to a monoexponential kinetics. In membranes from ileum, the calculated dissociation rate constants (kappa_ 1) were 0.0257 min-1 and 0.0595 min-1, for [3H]-lacidipine and[3H]-isradipine, respectively.5. The non specific binding of [3H]-lacidipine and [3H]-isradipine, was measured in intact rat aorta preparations incubated under the conditions of the functional experiments, in the presence of nifedipine(1 microM). After incubation with [3H]-lacidipine 77.6 +/- 1.9 pM for 2 h the concentration of drug in the tissue was 15.15 +/- 1.18 fmol mg-1 w.wt. and still amounted to 7.24 +/- 0.61 fmol mg-1 w.wt. after 3.5 h washout in drug-free solution. After incubation with [3H]-isradipine 47.2 +/- 0.4 pM for 2 h it was 2.26 +/-0.07 fmol mg-1 w.wt. and was undetectable after 3.5 h washout in a drug-free solution.6. It is concluded that lacidipine interacts reversibly with dihydropyridine binding sites and that the apparent irreversible inhibition of contraction in depolarized preparations could be related to a nonspecific binding in a tissue compartment different from the plasma membrane.

Animals↗

PubMed1991

The use of calcium antagonists to treat intra-operative hypertension--evaluation of efficacy and safety of a new dihydropyridine derivative, intravenous isradipine, during abdominal surgery.

Twenty-three patients who developed intraoperative hypertension (mean arterial pressure greater than 110 mmHg) during abdominal surgery under balanced general anaesthesia were randomly assigned to two groups. The isradipine group (n = 12) received 0.5 mg of isradipine, and the placebo group (n = 11) received 10 ml of isradipine solvent over a 5-min period in a blind manner. Arterial pressure was recorded 12 min after the injection was started. If the mean arterial pressure had not decreased by at least 10% at 12 min, patients received in an open manner 0.5 mg of isradipine. None of the patients in the isradipine group received isradipine in an open manner, in contrast with nine of the 11 patients in the placebo group (P less than 0.0001, Fisher's exact test). During both the blind period and the open trial, isradipine induced a 40% decrease in systolic, diastolic, and mean arterial pressures within the first two min of infusion. Arterial pressure remained below the pre-isradipine injection values for at least 45 min. Transient hypotension (mean arterial pressure less than 70 mmHg) was noted in 6/21 patients (29%). Mean heart rate remained statistically unchanged during the decrease in arterial pressure in both groups, but a tachycardia (increase in heart rate greater than 20 beats min-1) was noted in 4/21 patients (19%). This study indicates that intravenous isradipine is an effective therapy with sustained efficacy for intraoperative hypertension during abdominal surgery. The safety of its use needs a close monitoring of arterial pressure.

Abdomen↗

PubMedDate not supplied

Comparative effects of the calcium antagonist isradipine and some other dihydropyridine derivatives on regional blood flow in anesthetized open-chest dogs.

The effects of isradipine (PN 200-110), isopropyl 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2,6-dim ethyl-3- pyridinecarboxylate, on some cardiovascular parameters and regional blood flow were compared with those of other dihydropyridine derivatives in anesthetized open-chest dogs. Intravenous (i.v.) administrations of isradipine 3 and 10 micrograms/kg, nifedipine 10 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, decreased aortic blood pressure and increased aortic (AoF), vertebral (VBF) and coronary blood flow (CBF), but did not affect heart rate and left ventricular end-diastolic pressure. Renal blood flow was reduced by isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg, but was not influenced by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg. Left ventricular dP/dt was increased by isradipine 3 micrograms/kg, nicardipine 10 micrograms/kg and nisoldipine 10 micrograms/kg, but remained essentially unchanged following isradipine 10 micrograms/kg and nifedipine 10 micrograms/kg. The increase in AoF, VBF and CBF lasted 5-9 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nifedipine 10 micrograms/kg or nicardipine 10 micrograms/kg, 17-30 min following nisoldipine 10 micrograms/kg, and 16-44 min following isradipine 3 micrograms/kg i.v., but persisted for at least 60 min following isradipine 10 micrograms/kg. Under the experimental conditions and at the doses used in this study, all 4 drugs reduced total peripheral resistance as well as resistance in the vertebral, coronary and renal vascular beds. The results suggest that isradipine exerts cardiovascular effects similar to other calcium antagonists of the dihydropyridine group, but possesses a longer duration of action and shows a greater specificity in reducing coronary vascular resistance than nifedipine, nicardipine and nisoldipine.

Anesthesia↗