Once daily amlodipine in the treatment of mild to moderate hypertension.

1. The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo controlled parallel group study. The dose range of amlodipine was 2.5-10 mg daily titrated at 2 weekly intervals for a total treatment period of 8 weeks. 2. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. 3. Blood pressure returned to baseline values during a terminal 4 week washout period on placebo. 4. There were no significant effects on heart rate. 5. Two patients experienced slight ankle oedema while receiving amlodipine 10 mg daily but the active drug was otherwise well tolerated. 6. Plasma concentration of amlodipine, sampled 24 h after the preceding dose, increased as the dose titration sequence was followed, averaging 2.5 ng ml-1 on 2.5 mg, 4.9 ng ml-1 on 5 mg and 10.5 ng ml-1 on 10 mg.     

Amlodipine in hypertension: its effects on platelet aggregation and dynamic exercise

The antihypertensive efficacy and safety of once-daily amlodipine (5-10 mg) were studied in patients with essential hypertension. The study also included an assessment of the effects of single doses of amlodipine on platelet aggregation. Ten patients received amlodipine (mean daily dose of 7 mg) for 12 weeks in an open chronic study preceded by a 4-week placebo run-in period. Amlodipine significantly reduced the mean dorsal supine (-31/-20 mm Hg), sitting (-34/-23 mm Hg), standing (-34/ -23 mm Hg), and postexercise (-30/-20 mm Hg) blood pressures (BPs) at the end of 12 weeks of treatment compared with the placebo run-in period (p < 0.005), with no significant change in heart rate. At the end of a 4-week placebo washout phase following the chronic study, nine of the patients received an acute single 10-mg dose of amlodipine. Exercise testing before and 6 h after dosing showed that an acute 10 mg dose of amlodipine reduced BP without modifying the physiologic response to dynamic exercise. Amlodipine significantly reduced the degree of platelet aggregation in these patients (p < 0.005) induced by either collagen or ADP. This study demonstrated that amlodipine once daily was an effective antihypertensive agent and significantly inhibited platelet aggregation.     

The efficacy and safety of amlodipine in the treatment of mild and moderate essential hypertension in general practice

The antihypertensive efficacy and safety of amlodipine was evaluated in an open, multicenter general practice study. Hypertensive patients with sitting diastolic blood pressure in the range 95-115 mm Hg entered an initial 2-week baseline period during which they received placebo in a single-blind fashion. The dose of any concomitant antihypertensive treatment was kept constant for 4 weeks prior to baseline evaluations and throughout the study. Patients with an average sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg at two consecutive visits during the baseline period continued to the 8-week dose adjustment phase of the study. Patients were started on 5 mg of amlodipine once daily adjusted after 4 weeks to 10 mg once daily to achieve a target sitting diastolic blood pressure < or = 90 mm Hg. Amlodipine treatment produced significant falls in blood pressure (-23.7/-17.3 mm Hg; p < 0.05) with no effect on heart rate. Amlodipine was well tolerated, with most adverse events being mild or moderate. Investigators' global evaluation of toleration was excellent or good in 92% of patients. Subgroup analysis showed amlodipine to be equally efficacious and well tolerated in elderly or young patients, and in patients taking amlodipine as monotherapy or combination therapy.     

An open multicenter efficacy and safety evaluation of amlodipine in the treatment of symptomatic myocardial ischemia

The efficacy and safety of amlodipine (5-10 mg) once daily were studied in an open study in patients with symptomatic myocardial ischemia. The study is ongoing and this report is based on an interim analysis of data from 78 patients. A 2-week baseline period in which patients maintained their current antianginal therapy was followed by a 10-week treatment period with 5-10 mg of amlodipine/day. Both the median number of angina attacks per week and the median number of nitroglycerin (NTG) tablets consumed/week were significantly reduced after amlodipine (mean daily dose of 8.6 mg) when compared with baseline (p < 0.05). A total of 98.4% of patients (63/64) experienced a reduction in the frequency of angina attacks/week and 91% of patients (58/64) had angina attacks reduced to < or = 2/week. In self-assessments, 95% of patients (55/58) reported improved angina control and 91% (53/58) felt their ability to perform usual activities had improved. Twenty-seven patients experienced adverse events reported as drug related. The most common adverse event noted was edema. Amlodipine once daily significantly reduced the incidence of angina attacks and the concomitant need of nitroglycerin for relief of symptoms and thus improved the patients' ability to perform daily activities. Most adverse events reported were mild or moderate and the incidence is as would be expected in this patient population.     

Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

Open evaluation of amlodipine in the monotherapeutic treatment of systolic hypertension in the elderly

The antihypertensive efficacy and safety of amlodipine (5-10 mg once daily for 10 weeks) was assessed in elderly patients with primary systolic hypertension (average sitting and standing systolic blood pressure > or = 160 mm Hg and diastolic blood pressure < or = 95 mm Hg). Interim analysis of data from 25 patients shows that amlodipine treatment produced significant decreases in sitting blood pressure (-26.8/-11.4 mm Hg; p < 0.05). Efficacy assessments after 8 weeks of therapy showed 15 of 21 (71.4%) evaluable patients were considered therapeutic successes with amlodipine (defined as a fall from baseline in sitting systolic blood pressure of > or = 20 mm Hg or to < or = 150 mm Hg with a fall of > or = 10 mm Hg). Of the six evaluable patients who were not considered therapeutic successes using this definition, three had clinically beneficial falls in systolic blood pressure of 16-18 mm Hg. Fourteen patients were considered therapy successes on the basis of assessments taken 48 h postdose at the end of the study. Investigators' overall impression of efficacy was excellent or good in 21 patients (84%). Amlodipine treatment had no significant effect on heart rate. Amlodipine was generally well tolerated, with no patients being withdrawn due to side effects. Investigators' evaluation of toleration was excellent or good in 22 patients (88%).     

Effect of amlodipine on 24-hour ambulatory blood pressure in hypertensive patients

Sixteen hypertensive patients (diastolic blood pressure of 95-114 mm Hg) were randomized to receive 5 mg of amlodipine daily or placebo, double blind, for 4 weeks. Antihypertensive efficacy was assessed using ambulatory blood pressure monitoring at baseline and following double-blind therapy in conjunction with sphygmomanometric measurement at 2-week intervals. Laboratory tests, ECG, and adverse effects were recorded to assess tolerability. Amlodipine treatment significantly reduced ambulatory blood pressure without altering the normal circadian variation throughout the monitoring period. Supine and standing blood pressure were significantly reduced by amlodipine 24 h postdose. Amlodipine was well tolerated and was not associated with reflex tachycardia.     

Efficacy and Tolerability of Amlodipine in the General Practice Treatment of Essential Hypertension in an Asian Multinational Population

OBJECTIVE: To evaluate the efficacy and tolerability of once-daily amlodipine (Pfizer Pharmaceuticals Inc.) alone or in combination with other antihypertensive drugs in an Asian population with essential hypertension. PATIENTS: An open study was undertaken in 165 male and 158 female patients with uncomplicated hypertension (diastolic blood pressure 95 to 115mm Hg). Patients were recruited from 41 general practices in seven Asian countries and received amlodipine 5mg daily for 4 weeks and then 10mg once daily for a further 4 weeks if the target diastolic blood pressure of /=10mm Hg had not been achieved. This one-step dose-adjustment period was followed by a 4-week maintenance period on a constant dose. Amlodipine was the sole medication in 284 patients and was added to other antihypertensive drugs in 39 patients uncontrolled on previous medication. RESULTS: 263 patients, including 131 males, were evaluated for efficacy at the final treatment visit. 166 (63%) patients achieved the target reduction in diastolic blood pressure with amlodipine 5mg once daily, while 84 patients achieved the target reduction with 10mg once daily. Systolic and diastolic blood pressure reductions were similar irrespective of gender or age, and there were no significant changes in resting heart rate in any subgroup. In 68 patients who underwent ambulatory monitoring, the systolic and diastolic blood pressures were reduced by once-daily amlodipine throughout the 24-hour period without change in the intrinsic circadian pattern. Amlodipine was well tolerated in all patient subgroups; adverse events accounted for less than 1% of treatment discontinuations, and there were no hospitalisations or deaths during the study. Investigators rated both the antihypertensive efficacy and tolerability of amlodipine as excellent or good in 93% of patients. CONCLUSION: In 263 Asian patients with uncomplicated essential hypertension treated in general practice, once-daily amlodipine in a dose of 5 or 10mg provided significant antihypertensive efficacy either as monotherapy or in combination with other antihypertensive drugs while maintaining a favourable tolerability profile regardless of gender or age.     

An open, parallel, comparative evaluation of amlodipine and nitrendipine in the monotherapeutic treatment of mild and moderate essential hypertension

The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.     

苯磺酸氨氯地平治疗老年高血压128例疗效观察

目的观察苯磺酸氨氯地平对老年高血压的治疗效果。方法选取128例老年高血压患者每天口服5mg氨氯地平1次,连续4～8周,测量治疗前后血压情况。结果4周后,显效79例（61.7%）,有效45例（35.2%）,总有效率为96.9%;与治疗前相比,苯磺酸氨氯地平治疗后收缩压和舒张压水平显著降低。结论苯磺酸氨氯地平是治疗老年高血压的理想药物。     

24-hour blood pressure control with the once-daily calcium antagonist amlodipine

The efficacy and toleration of once-daily amlodipine (5-10 mg) was studied in 11 patients with mild to moderate hypertension. Continuous intra-arterial blood pressure monitoring was used to study the effects of amlodipine over a 24-h period. Following a 2-week placebo run-in period, amlodipine was given initially as a single-blind 5-mg dose for 2 weeks and increased to 10 mg if required to control blood pressure for a further 4 weeks. Twenty-four-hour intra-arterial blood pressure recordings made after 6 weeks of treatment with amlodipine revealed that amlodipine effectively reduced blood pressure throughout the whole 24-h period without altering the normal circadian pattern. The mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (p < 0.05) and the mean nighttime blood pressure was reduced from 137/79 to 121/69 mm Hg (p < 0.05). There was no significant change in heart rate. The mean supine blood pressure measured sphygmomanometrically was reduced from 169/103 mm Hg after placebo to 153/98 mm Hg after 2 weeks of treatment and to 145/92 mm Hg at the end of the study. The results of isometric and dynamic exercise testing showed that amlodipine decreased blood pressure, with no postural decrease on tilting and no change in the proportional increase in blood pressure at peak exercise. Amlodipine was well tolerated although one patient developed ankle edema that would have required discontinuation had she not already completed the study. This study has shown that amlodipine effectively reduced blood pressure for 24 h after once-daily dosing and was well tolerated.     

A comparison of amlodipine with enalapril in the treatment of moderate/severe hypertension.

1. The safety and efficacy of amlodipine vs enalapril as monotherapy was evaluated in patients with moderate/severe hypertension (supine DBP 105-125 mm Hg, SBP 140-220 mm Hg). 2. After 2 weeks placebo treatment 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (15 patients) 5-10 mg, or enalapril (16 patients) 5-20 mg for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Clinic supine systolic blood pressure was reduced from 177 to 152 mm Hg (amlodipine) and 183 to 169 mm Hg (enalapril) (95% CI for the intergroup difference -22.1, 0.3, P = 0.06) after 8 weeks treatment. 4. Clinic supine diastolic blood pressure was reduced from 110 to 93 mm Hg (amlodipine) and 109-102 mm Hg (enalapril) (95% CI for the intergroup difference -17.7, -2.7, P < 0.01) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure. Although the reduction in blood pressure was greater for the amlodipine treated group, the differences between treatments were not statistically significant. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (5), peripheral oedema (3), upper respiratory infection (3) and anxiety (2). The adverse events occurring most frequently in the enalapril treated patients were headache (6), dizziness (3) and upper respiratory infection (2).     

24 h blood pressure control with the once daily calcium antagonist, amlodipine.

1. Amlodipine is a novel calcium antagonist which, although pharmacologically similar to other dihydropyridine calcium antagonists, has a long plasma half-life, permitting steady state blood levels to be achieved with a once-daily dose regimen. 2. We have performed a study to examine the effects of this drug on the blood pressure of hypertensive patients over a 24 h period. After a placebo run-in, the drug was administered to 11 patients at a starting dose of 5 mg, and increased to 10 mg after 2 weeks of treatment if the cuff diastolic blood pressure response was unsatisfactory. Cuff measurements were made at entry, after 2 weeks treatment with placebo, after 2 weeks on amlodipine 5 mg once daily, and after a further 4 weeks on amlodipine 5 mg or 10 mg once daily. Intraarterial blood pressure recordings were made at the end of the placebo phase and at completion of the study. 3. Mean supine blood pressure measured sphygmomanometrically was 168/103 (n = 11) mm Hg at entry, 169/104 (n = 11) mm Hg at the end of the placebo phase, 153/95 (n = 11) mm Hg after 2 weeks of treatment and 146/92 (n = 11) mm Hg at the end of the study. Blood pressure curves plotted for each phase of the study revealed an effective 24 h duration of action. Mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (P less than 0.05, n = 10), and mean night-time blood pressure was reduced from 137/79 to 121/69 mm Hg (P less than 0.05, n = 10).(ABSTRACT TRUNCATED AT 250 WORDS)     

An 8-week double-blind study of amlodipine and diltiazem in patients with stable exertional angina pectoris

A multicenter, double-blind study was performed to compare the antianginal efficacy and safety of the new dihydropyridine calcium antagonist amlodipine with the benzothiazepine calcium antagonist diltiazem in patients with stable exertional angina pectoris. Following a 2-week placebo run-in period, 39 patients were randomized to receive amlodipine (2.5-10 mg once daily) and 41 patients to receive diltiazem (60-120 mg three times daily) in an 8-week double-blind treatment phase. The study used standardized bicycle exercise testing as a primary efficacy assessment. Patients also recorded angina frequency and nitroglycerin (NTG) tablet consumption/ week. Treatment with amlodipine and diltiazem resulted in an improvement in total exercise time, time to angina and total work, mean ST-segment deviation at maximum common load, median number of angina attacks/week, and NTG tablet consumption/week. The incidence and severity of possibly treatment-related side effects and laboratory test abnormalities were comparable for both drugs. The most frequently reported side effects were dizziness, headache, peripheral edema, and nausea. Two patients withdrew from diltiazem treatment due to pruritus in one case and severe headache and moderate dyspnea in the other. No amlodipine-treated patients withdrew due to side effects. In conclusion, this study demonstrated that the antianginal efficacy and tolerability of amlodipine is equivalent to diltiazem, but amlodipine has the advantage of once-daily dosing.     

Efficacy, tolerability, and impact on quality of life of long-term treatment with manidipine or amlodipine in patients with essential hypertension

This double-blind, multicenter trial compared antihypertensive efficacy, tolerability, and impact on quality of life of manidipine and amlodipine in patients with mild-to-moderate essential hypertension. Patients were randomly assigned to 48 weeks of once-daily manidipine, 10-20 mg, or amlodipine, 5-10 mg. Patients who did not respond to treatment after 12 weeks were also given enalapril, 10-20 mg, for the study's duration. The main efficacy end point was equivalence in sitting systolic (SiSBP) and diastolic (SiDBP) blood pressure reduction between the two drugs after 8 weeks (per protocol analysis). An intention-to-treat (ITT) analysis was performed in all patients with at least one efficacy determination during treatment. Quality of life was assessed by the "Subjective Symptoms Assessment Profile" (SSA-P) and "General Well-being Schedule" (GWBS), after 12 weeks of treatment. SiSBP reduction after 8 weeks was equivalent for manidipine (15.2 mm Hg, n = 227) and amlodipine (17.0 mm Hg, n = 219). The corresponding figure for SiDBP was 11.3 mm Hg for manidipine and 12.3 mm Hg for amlodipine. In the larger ITT population SiDBP was similarly and significantly reduced by manidipine (from 102 +/- 5 to 88 +/- 9 mm Hg, n = 241) and amlodipine (from 101 +/- 5 to 87 +/- 8 mm Hg, n = 240). Similar results were observed for SiSBP and standing SBP and DBP. Neither drug changed sitting or standing heart rate compared with baseline. SSA-P scores improved with manidipine but not amlodipine. GWBS total and partial scores increased more with manidipine than with amlodipine. Safety profile favored manidipine, which was associated with significantly less ankle edema than was amlodipine. This study shows for the first time that long-term treatment with the long-acting calcium channel blocker manidipine is as effective as treatment with amlodipine, has a better tolerability profile, and induces greater improvement in quality of life than amlodipine.     

A double-blind, parallel, comparative evaluation of amlodipine vs. captopril in the monotherapeutic treatment of mild and moderate essential hypertension

A double-blind, parallel, comparative study of the antihypertensive efficacy and safety of once-daily oral doses of amlodipine (5-10 mg/day) vs. twice-daily oral doses of captopril (25-50 mg twice daily) in adult patients with mild or moderate essential hypertension (supine diastolic blood pressure of 95-115 mm Hg) was undertaken in two hospital centers. Interim analysis of data from 40 patients shows that amlodipine and captopril both significantly (p < 0.05) reduced blood pressure compared with baseline. Nineteen of 21 (90.5%) amlodipine-treated patients and 15 of 19 (78.9%) captopril-treated patients had their diastolic blood pressure "normalized" (< 90 mm Hg) with mean final doses of 8.2 and 76.7 mg/day, respectively. At the final visit, there were no statistically significant differences between the two treatment groups in either mean supine or standing blood pressure. Minor nonsignificant changes in standing heart rate were observed in both treatment groups. Seven of the 21 amlodipine-treated patients and 3 of the 19 captopril-treated patients reported adverse experiences. No patients in either treatment group discontinued due to adverse events; one patient in the amlodipine group required a dose reduction. These interim data indicate that the overall efficacy and safety profiles of these two drugs are comparable.     

A 6-week double-blind comparison of amlodipine and placebo in patients with stable exertional angina pectoris receiving concomitant beta-blocker therapy

This study was a multicenter, double-blind comparison of the antianginal efficacy and safety of amlodipine and placebo as adjunctive therapy with constant recommended maintenance doses of beta-blockers. Patients with stable exertional angina pectoris were randomized to placebo or amlodipine at a starting dose of 5 mg once daily. The amlodipine dose was adjusted to 10 mg daily after 2 weeks if angina attacks were not abolished. Antianginal efficacy was assessed throughout the study with angina diaries, investigators' and patients' global evaluations, and with bicycle exercise tests during a placebo run-in period (baseline) and after 2 and 6 weeks of double-blind treatment. On baseline-final analysis, the exercise time to angina onset increased by 13% with amlodipine compared to 6% with placebo (p < 0.05). The total exercise time increased by 11% on amlodipine compared with 2% on placebo, though this difference did not reach statistical significance. Angina attack frequency and nitroglycerin consumption were both reduced by adding amlodipine to beta-blocker treatment. Amlodipine in combination with beta-blocker therapy was well tolerated, with a low incidence of side effects and laboratory test abnormalities. The study showed clearly that addition of amlodipine to beta-blocker therapy in patients with stable angina pectoris was well tolerated and gave improved antianginal efficacy.     

Randomized, double-blind, crossover comparison of amlodipine and valsartan in african-americans with hypertension using 24-hour ambulatory blood pressure monitoring

STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.     

Effects of new calcium channel blocker, azelnidipine, and amlodipine on baroreflex sensitivity and ambulatory blood pressure

The effect of dihydropyridine calcium channel blocker (CCB) on baroreflex sensitivity (BRS) is not well described. We studied the effect of a new CCB, azelnidipine, compared with amlodipine, on BRS and ambulatory blood pressure (BP) in newly diagnosed untreated hypertension. This study was a prospective, randomized, and open-label study. We randomized patients to either azelnidipine or amlodipine treatment. Azelnidipine 8 to 16 mg (average 14.5 mg) and amlodipine 2.5 to 7.5 mg (average 4.9 mg) were used to lower the clinical BP <140/90 mm Hg. BRS, evaluated by the spontaneous and the Valsalva methods, and clinical and ambulatory BP were evaluated at baseline and after 13 weeks of each treatment. A total of 47 patients (age 53.1 +/- 10.8 years, 51% male), 26 in the azelnidipine group and 21 in the amlodipine group, completed the study. For baseline and after therapy respectively, both Valsalva-BRS (4.8 +/- 1.7 vs. 8.4 +/- 3.1 msec/mm Hg, P = 0.001) and spontaneous-BRS (5.5 +/- 2.5 vs. 8.2 +/- 5.6 msec/mm Hg, P = 0.019) were increased by azelnidipine, but amlodipine did not change them. Clinical and awake BPs were similarly reduced by each drug therapy. In conclusion, BRS was increased by azelnidipine therapy, but not by amlodipine therapy. This differential effect may be important in cardiovascular risk reduction.     

The antinociceptive effect of leukotriene D(4) receptor antagonist, MK-571, in mice: possible involvement of opioidergic mechanism

The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.