Effects of Daurisoline on L-Type Calcium Channel CaV1.2 Expressed in HEK293 Cells / 中国药师

Objective:To investigate the effects of daurinsoline (DS) on L-type calcium channel Cav1.2 expressed in HEK293 cells.Methods:Cav1.2 was transferred into HEK293 cells using Lipofectamine 2000, and the effects of DS on Cav1.2 currents (ICav1.2) were analyzed by whole-cell patch clamp techniques. Results:DS at 1,3 and 10 μmol·L-1could inhibit the ICav1.2in HEK293 cells in a dose-dependent manner. The inhibitory rate was(14.68 ± 4.02) %,(32.37 ± 6.63) % and(59.63 ± 5.23) %,respectively. The inhibitory rate of DS at 3 μmol·L-1was 40 % of that of 3 μmol·L-1isradipine(a L-type calcium channel blocker). Conclusion:DS can inhibit the ICav1.2in HEK293 cells in a dose-dependent manner and the inhibition of DS is weaker than that of isradipine.

Estudo multicêntrico brasileiro de avaliaçäo de eficácia clínica e tolerabilidade da isradipina SRO através da monitorizaçäo ambulatorial da pressäo arterial no tratamento da hipertensäo arterial leve e moderada / Tolerability and Antihypertensive Effects of Isradipine SRO on Clinical and Ambulatorial Blood Pressure Monitoring in Essential Hypertensives. A Brazilian Multicenter Study

PURPOSE--To evaluate clinical efficacy and tolerability of isradipine SRO (I.SRO), 5 mg O.D. in essential hypertensives. METHODS--Eighty-three of 87 selected outpatients with a mean age of 51.3 years (ranging from 25 to 65), 33 male, 48 white, 29 black and others of different races, who had clinical supine and orthostatic diastolic blood pressure (DBP) > or = 95 mmHg and < or = 115 mmHg underwent the study. After a three-week wash-out period, patients received I.SRO 5 mg O.D. at 8:00 am for a six-week period (phase I). After this phase, patients received I.SRO 5 mg O.D. at 8:00 pm for a six-week period (phase II). The patients had a follow-up with an interval of three weeks and the ambulatorial blood pressure monitoring (ABPM) for 24 hours was performed with a SpaceLabs 90207 or Del Mar Avionics devices after the wash-out period and at the end of phases I and II. Measurements were performed at 15-min intervals during the day (6 am to 10 pm) and at 30-min intervals during the night (10 pm to 6 am). RESULTS--a) Heart rate did not show significant changes during the treatment period (phases I and II) when compared with the wash-out period; b) causal blood pressure: at the end of both treatment periods (phases I and II) there were statistically significant decreases (p < 0.001) in supine SBP and DBP compared with wash-out values. The mean SBP decreased from 161.6 +/- 14 to 144.3 +/- 13 mmHg (phase I) and to 141.8 +/- 13 mmHg (phase II). The mean DBP decreased from 103.4 +/- 6 to 91.2 +/- 7 (phase I) and to 89.1 +/- 8 (phase II); c) ABPM: the mean systolic 24-h ambulatory blood pressure was significantly reduced (p < 0.001) from 148.8 +/- 17 to 137.2 +/- 15 mmHg (phase I) and to 133.4 +/- 13 mmHg (phase II). The mean diastolic 24-h ambulatory blood pressure was significantly decreased (p < 0.001) from 94.3 +/- 9 to 87.0 +/- 9 (phase I) and to 85.8 +/- 8 mmHg (phase II). The mean daytime and nighttime, systolic and diastolic 24-h ambulatory blood pressure were: wash-out--152.3 +/- 17, 140.2 +/- 21, 97.4 +/- 9, 86.8 +/- 13; phase I--139.9 +/- 15, 130.0 +/- 17, 89.3 +/- 9, 81.3 +/- 10; phase II--136.7 +/- 13, 125.3 +/- 15, 88.5 +/- 8, 79.1 +/- 10, respectively. Blood pressure load (percentage of systolic blood pressure values > 140 mmHg or of diastolic blood pressure values > 90 mmHg) was significantly reduced from 62.2/62 per cent (SBP/DBP), on the was-out, to 37.9/39.9 per cent (SBP/DBP) on phase I and to 32.3/34.3 per cent (SBP/DBP) on phase II; d) side effects: most frequently related were palpitations (2.3 per cent ), headache (1.1 per cent ), flush (1 per cent ) and ankle oedema (1 per cent ). They were in general, mild-to-moderate and disappeared after the first 3 weeks of treatment. Only two patients were withdrawn because of headache (one of them with previous diagnosis of migraine). CONCLUSION--I.SRO, given by oral route, in the dosage of 5 mg O.D. as monotherapy, was effective and well tolerated, promoted significant reduction on 24-h ambulatory blood pressure attenuating the early morning rise and did not interfere with the circadian rhythm of blood pressure. No significant differences were detected in the BP lowering effect when I.SRO was given during the morning or evening. These results may indicate that the drug is as suitable as one of the first choice for treating mild and moderate hypertensive patients

Antihypertensive Effects and Safety of Isradipine in Patients with Essential Hypertension

BACKGROUND: Antihypertensive treatment represents the modification of one of the most important risk factors on the development of cardiovascular, cerebrovascular and peripheral vascular disease. In cases of markedly developed atherosclerosis, reduction of blood pressure can improve the survival of patients by reducing the incidence and/or severity cerebrovascular events. We studied a new dihydropyridine calcium antagonist isradipine to evaluate the efficacy and safety in patients with essential hypertension. METHOD: After a placebo run-in phase of four weeks duration, 2.5mg isradipine once daily orally was administered for four weeks to 84 patients (48 males, 36 females ; mean age ; 50.8 years). And then 5.0mg isradipine once daily was administered for four weeks to 59 patients whose diastolic pressure did not decrease less than 90 mmHg. RESULTS: 1) At the end of 8 weeks of therapy, systolic and diastolic blood pressure were significantly reduced from 158.2+/-11.5/101.7+/-5.1mmHg in sitting, 156.8+/-13.7/102.3+/-5.6mmHg in standing to 138.3+/-13.8/90.1+/-6.7mmHg in sitting, 137.6+/-13.7/91.2+/-7.6mmHg in standing (p<0.001). And the effectiveness rate was 84.3% in sitting, 83.2% in standing and normalization rate below 90mmHg in diastolic pressure was 67.5% in siting and 61.5% in standing position. 2) The sitting and standing pulse rate did not change significantly (72.7+/-7.4beats/min at baseline vs. 73.4+/-6.8 beats/min after 8 weeks trial in sitting, 73.5+/-7.2beats/min at baseline vs. 74.1+/-7.2 beats/min after 8 weeks trial in standing). 3) The reduction of mean systolic and diastolic blood pressure at the end of 8 weeks were 19.9/11.6mmHg in sitting and 19.2/11.1mmHg in standing. 4) At the end of 8 weeks the successes of therapy in sitting were 67.5% in excellent, 10.8% in good, and 6.0% in fair response. 5) There was no serious side effect except mild symptom of 5 cases(5.9%) of exertional dyspnea and one episode of (1.2%) tachycardia. CONCLUSION: These results indicate that isradipine is effective and safe antihypertensive agent in the treatment of essential hypertension.

Tratamento da crise hipertensiva em pacientes ambulatoriais com isradipina sublingual / Outpatients hypertensive crisis therapy with isadipine by sublingual route

Objetivo - Avaliar a eficácia clínica e a tolerabilidade da isradipina, um novo antagonista do cálcio hipertensiva. Casuística e Métodos - Foram estudados vinte e sete pacientes (14 brancos, 13 näo brancos) com idades variando entre 18 e 59 (média 37,2 ñ 2,5) anos; 15 homens, 13 mulheres cujas pressöes arteriais diastólicas eram superiores a 130 mmHg e que näo apresentavam sinais recentes de lesöes agudas em órgäos-alvo. Estes pacientes foram divididos em três grupos aos quais se administraram diferentes doses de isradipina na forma de comprimidos por via sublingual, conforme segue: grupo I - (n = 10) 1,25 mg; grupo II - (n = 10), 2,5 mg; grupo III - (n = 7) 5,0 mg. A pressäo arterial (PA) e a freqüência cardíaca (FC) dos pacientes foram medidas antes da administraçäo da droga e depois a cada 30 minutos até o máximo de 120 minutos. Resultados - A pressäo arterial média (PAM) reduziu-se significativamente em todos os pacientes 153,43 ñ 4,3 mmg para 124,0 ñ 2,3 mmHg após 60 min de administraçäo da droga e, para 118 ñ 2,1 mmHg após 120 min do seu uso (p < 0,001). A FC näo apresentou variaçöes clinicamente significativas. Näo se observaram também efeitos colaterais limitantes do uso da droga nas doses empregadas. A comparaçäo entre as curvas de variaçäo da PAM dos três grupos näo apresentou diferenças significantes, tendo-se observado, entretanto, uma tendência a maior velocidade de descenso da PA nos pacientes do grupo III. Conclusäo - Os resultados evidenciam que a isradipina administrada na forma de comprimidos por via sublingual, nas doses de 1,25, 2,5 e 5,0 mg reduz eficazmente a PA de pacientes com crise hipertensiva sem a ocorrência de efeitos colaterais importantes. O início de açäo da droga foi rápida (30 min) após a administraçäo e o descenso máximo da PA foi observado após 2h. Näose observaram também reduçöes dose-dependentes da PA

Purpose - Evaluate the efficacy and tolerability of isradipine, a new dihydropyridine calcium antagonist in the therapy of outpatients hypertensive crisis. Patients and Methods - Twenty seven patients with mean age of 37.2 ± 2.5 years (ages ranging from 18 to 59 years old ) of different races (14 white, 13 not white); 15 men and 12 women, with diastolic blood pressure over 130 mmHg and without signs of recent target organ damage were studied. The patients were divided in three groups according to the used dosage of Isradipine tablets by sublingual route. Group I (n = 10): 1.25 mg; Group II (n = 101:2.5 mg and Group III (n = 7): 5.0 mg. Arterial blood pressure levels and heart rate were determined before the drug administration and every 30 minutes until 120 minutes after dosing. Results - Mean arterial blood pressure (MABP) decrease significantly in all patients from 153.43 ± 4.3 to 124.0 ± 2.3 mmHg after 60 minutes and to 118.0 ± 2.1 mmHg after 120 minutes (p < 0.001). Heart rate did not show significant changes with the drug. Clinical significant side effects were not observed. The comparative analysis of MABP curves did not show significant differences among the groups I, II and III. However, a tendency of a greater decrease in MABP was observed in the patients of group III. Conclusion - Isradipine tablets in the dosages of 1.25, 2.5 and 5.0 mg by sublingual route is effective and well tolerated in the treatment of ambulatorial patients with hypertensive crisis

A Study of Antihypertensive Effect of Isradipine(Dynacirc)

Essential hypertension is an important public health problem in Korea-being common, asymptomatic, easily treatable, and often leading to lethal complication in left untreated. The number of patients with hypertension has been significantly increased, and this factor may be an importnat one responsible for the increase in cardivascular mortality during past 20 years in Korea. As the drug therapy for hypertension needs longer period, it is very important to evaluate the efficacy and the adverse effects. Thirty patients(17 men and 13 womon) with essential hypertension were evaluated in this study. All patients had received oral Isradipine 1.25~2.5mg b.i.d. for 8 weeks. 1) The systolic and diastolic pressure were decreased significantly(166.8+/-9.0mmHg vs 147.3+/-12.0mmHg, p<0.001 and 100.3+/-4.0mmHg vs 90.3+/-6.1mmHg, p<0.001, respectively) 2) Heart rate, body weight, laboratory tests, chest X-ray, ECG studies were not changed significantly. 3) The systolic pressure was lowered by 20mmHg or more in 17 cases(56.7% of total), and the diastolic pressure was lowered by 10mmHg or more in 20 cases(66.7% of total) at 8 weeks after Isradipine administration. 4) The adverse effects of Isradipine were edema in 3(10%), constipation in 2(6.7%), headache in 2(6.7%), and insomnia, dizziness and dry mouth in 1 patient respectively, and none of them discontinued Isradipine administration due to adverse effects. In many patients with essential hypertension there is an effective response to Isradipine, even though there may be some mild adverse effects.

Evaluation of the Efficacy and Tolerability of Isradipine in the Treatment of Mild to Moderate Hypertension

An open clinical trial was conducted to evaluate the efficacy and tolerability of isradipine in 30 cases (male 16, female 14 cases, average age 52.6+/-7.94) of mild to moderate essential hypertension using 1.25-2.5mg twice a day for 8 weeks of active treatment. Blood pressure was significantly reduced from 168.5+/-14.33/108.3+/-6.37mmHg, 163.7+/-9.74/105.5+/-7.1mmHg to 141.0+/-13.69/92.0+/-9.27mmHg, 138.8+/-13.46/92.3+/-11.16mmHg in sitting and standing position respectively. The extent of reduction was 27.5/16.3mmHg in sitting position and 29.9/13.2mmHg in standing position. This comprised the mean response rate in terms of reduction of DBP of 10mmHg or more being 90% and the normalization rate, deficed as DBP lowering to 90mmHg or below, being 70%. Heart rate, hematology and blood chemistry including blood sugar and lipids were not changed significantly after treatment with isradipine. No significantl side effect was observed except 2 cases of mild transient facial flushing and nausea during the treatment, so could proceed the trial without drug discontinuation in all 30 cases. The results suggest that isradipine is one of the useful and safe drugs in the treatment of mild to moderate essential hypertension.