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PubMed2004

Kinetic and cardiovascular comparison of immediate-release isradipine and sustained-release isradipine among non-treatment-seeking, cocaine-dependent individuals.

The authors sought to determine whether sustained-release (SR) isradipine provided comparable systemic availability to that of immediate-release (IR) isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR isradipine formulation and a 30-mg dose of an SR isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each isradipine dose administration. Neither the 15-mg dose of IR isradipine nor the 30-mg dose of SR isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR isradipine achieves a higher peak concentration than SR isradipine. The more favorable cardiovascular profile of SR isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.

Adult↗
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↗
PubMed2002

Isradipine treatment of hypertension in children: a single-center experience.

Many children with hypertension, particularly those with new-onset hypertension related to glomerulonephritis, organ transplantation, or other forms of secondary hypertension, require treatment with a short-acting antihypertensive in order to quickly achieve blood pressure (BP) control. We administered isradipine, a short-acting, second-generation calcium antagonist, to 72 such children. Retrospective data collection was undertaken to determine the effects of isradipine treatment. The mean age of children treated with isradipine was 74+/-55 months (mean+/-SD). Nearly all of these children had secondary hypertension and were initially treated as hospital inpatients for newly diagnosed hypertension. Mean isradipine dose was 0.36+/-0.17 mg/kg per day, with no significant variation in dose according to patient age. Isradipine was administered three times per day in most instances, but 21% of the time it was administered four times per day. An extemporaneous isradipine suspension was used in 62% of treatment courses. BP control was achieved with isradipine alone in 38 children; the remainder received isradipine in combination with additional antihypertensives. Comparison of pre-treatment BP with BP obtained 8+/-9 days later demonstrated a significant BP reduction with isradipine treatment, with a mean reduction of 14+/-13 mmHg for systolic BP and 13+/-15 mmHg for diastolic BP. There was no effect of isradipine treatment on heart rate. Adverse effects occurred in 9.5% of treatment courses, and included headache, flushing, dizziness, and tachycardia. We conclude that isradipine successfully lowers BP in hypertensive children with secondary forms of hypertension. Use of isradipine suspension allows infants and young children to be treated as readily as older children.

Adolescent↗
PubMed2000

Initial experience with isradipine for the treatment of hypertension in children.

BACKGROUND: Isradipine is a calcium channel blocker of the dihydropyridine class. It has limited effects on myocardial contractility; is available in a powder-filled capsule and has a half-life of 6 to 8 hours. METHODS: Pharmacy records were reviewed to identify pediatric patients who had received isradipine. The following demographic data were obtained: age, weight, sex, underlying medical problems, and initial blood pressure values. Information concerning isradipine included the initial dose and its interval, subsequent dose escalations, blood pressure response to the medication, and duration of therapy. RESULTS: The study population comprised 12 patients, ranging in age from 10 days to 11 years. The etiology of the hypertension was renal in 9 cases and nonrenal in 3. Initial dosing with isradipine was 0.1 mg/kg/dose. Six patients had emergent hypertension, and their blood pressure had been controlled with intravenous nicardipine before oral isradipine. Six patients received initial therapy with oral isradipine. Isradipine was monotherapy in 7 patients and in combination with other agents in 5 patients. The dose of isradipine required for blood pressure control was 0.6 +/- 0.3 mg/kg/day (range, 0.3 to 1.2 mg/kg/day). Isradipine failed to provide effective blood pressure control in 2 patients. In 1 of these patients, isradipine was effective after peritoneal dialysis. CONCLUSIONS: Isradipine is an effective, orally administered agent for control of hypertension in children.

Administration, Oral↗
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↗