amlodipine Norvasc
Amlodipine, a calcium channel inhibitor, and cocaine and ethanol's reinforcing effects.

Gardell LR, Reid ML, Cavallero CA, Burgess SE, Wallace RF, Hubbell CL, Reid LD.

Laboratory for Psychopharmacology, Rensselaer Polytechnic Institute, Troy, NY 12180-3590, USA.

The effects of amlodipine (from 0.1 to 3.0 mg/kg) on rats' pressing for rewarding brain stimulation, with and without cocaine administration, were assessed. None of the doses reliably modified the effects of cocaine. Also, amlodipine was given to two groups of rats taking alcohol: one group that was regularly taking a sweetened alcoholic beverage and the other taking an unsweetened alcoholic beverage. The only discernible effects of amlodipine on alcohol intake were associated with the highest dose and only with rats taking the sweetened beverage. The effects of this high dose could easily be attributable to behavioral toxicity elicited by the dose. In contrast, and confirming previous work, isradipine, another calcium channel inhibitor, produced reliable reductions on both cocaine's and alcohol's reinforcing effects. Despite the similarity of isradipine and amlodipine, isradipine apparently has some unique features with respect to cocaine and alcohol.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10548273&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Cardiovascular risk, renal hypertensive damage, and effects of amlodipine treatment in transgenic TGR(mREN2)27 rats.

Witte K, Schnecko A, Schmidt T, Voll C, Kranzlin B, Lemmer B.

Institute of Pharmacology and Toxicology, Faculty of Clinical Medicine, Mannheim, University of Heidelberg, Germany. witte rumms.uni-mannheim.de

Transgenic rats (TGRs) TGR(mREN2)27 are characterized by fulminant hypertension, an inverse circadian blood pressure rhythm, and severe hypertensive target organ damage. In the present study, we evaluated cardiovascular risk factors, renal function, and urinary protein loss in transgenic rats before and after treatment with the calcium channel blocker amlodipine. Amlodipine was injected intraperitoneally in a dose of 5 mg/kg/day, either once daily at 8.00 h or twice daily in divided doses at 8.00 and 20.00 h. Untreated TGRs and Sprague-Dawley rats served as hypertensive and normotensive controls, respectively. Before and after 5 weeks of treatment, rats were placed in metabolic cages for sampling of urine. Prior to treatment, urinary excretion rates of protein, albumin, and Ca2+ were significantly higher in TGRs than in Sprague-Dawley controls. Urinary excretion of protein and albumin was reduced by 5 weeks of amlodipine treatment, whereas the excretion of Ca2+ was not affected. The reductions in renal proteinuria and albuminuria by amlodipine treatment were significantly correlated with the treatment-induced decrease in blood pressure. These findings indicate that blood pressure itself is an important contributor to albumin loss by the kidney in renin-dependent hypertension of TGRs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10553884&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Differential effects of mibefradil, verapamil, and amlodipine on myocardial function and intracellular Ca(2+) handling in rats with chronic myocardial infarction.

Min JY, Sandmann S, Meissner A, Unger T, Simon R.

Department of Cardiology, University of Kiel, Germany.

Mibefradil is a selective T-type Ca(2+) channel blocker that exerts a potent vasodilating but weak inotropic action. The present study compared mibefradil with traditional L-type Ca(2+) channel blockers in regard to the effects of chronic oral administration on hemodynamics, contractility, and intracellular Ca(2+) handling in failing myocardium from postinfarction rats. Male Wistar rats with ligation-induced myocardial infarction were assigned to placebo or treatment with mibefradil (10 mg/kg/day), verapamil (8 mg/kg/day), or amlodipine (4 mg/kg/day) by oral gavage starting 7 days before the induction of myocardial infarction. Six weeks after myocardial infarction, hemodynamic measurements were performed in conscious animals. In addition, isometric force and free [Ca(2+)](i) were determined in isolated left ventricular papillary muscles. Placebo-treated rats exhibited a decreased mean atrial pressure, an increased left ventricular end-diastolic pressure, and a reduced rate of pressure rise compared with sham-operated animals. Mibefradil treatment significantly improved all of these parameters, whereas both amlodipine and verapamil exerted only minor effects. beta-Adrenergic stimulation with isoproterenol (ISO) enhanced contractility and Ca(2+) availability in papillary muscles from sham-operated rats, whereas the ISO-induced inotropic effect in muscles from placebo-treated rats was severely blunted. Chronic mibefradil treatment significantly improved the inotropic response to ISO stimulation, although the Ca(2+)(i) availability appeared to be less than in muscles from placebo-treated animals. In contrast, both verapamil and amlodipine did not restore the inotropic and Ca(2+)(i) modulating effect of ISO in remodeled myocardium. Thus, T-type Ca(2+) current appears to be of pathophysiological relevance in postischemic reperfused myocardium.

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amlodipine Norvasc
Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients.

Ahaneku JE, Sakata K, Urano T, Takada Y, Takada A.

Second Department of Physiology, Hamamatsu University School of Medicine, 3600 Handa-cho, Hamamatsu-shi, Shizuoka-ken, 431-3192, Japan,

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients. Copyright 2000 Academic Press.

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amlodipine Norvasc
Amlodipine enhances NO production induced by an ACE inhibitor through a kinin-mediated mechanism in canine coronary microvessels.

Zhang X, Xu X, Nasjletti A, Hintze TH.

Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.

Our previous study found that angiotensin-converting enzyme (ACE) inhibitors and amlodipine induce NO release from coronary microvessels through a kinin-dependent mechanism. The goal of this study was to determine whether amlodipine could potentiate NO formation during ACE inhibition. Coronary microvessels were isolated from 16 mongrel dogs. Nitrite, the hydration product of NO, from coronary microvessels was quantified by using the Griess reaction. Bradykinin and kallikrein all significantly increased nitrite release from coronary microvessels in a concentration-dependent manner. The ACE inhibitor, ramiprilat, potentiated these effects. Amlodipine also markedly potentiated nitrite production by ramiprilat. For instance, amlodipine (10(-10) M) enhanced nitrite release induced by ramiprilat (10(-7) M) from 122 +/- 9 to 168 +/- 14 pmol/mg (p < 0.05 vs. ramiprilat). Nitrite release potentiated by ramiprilat and amlodipine was entirely blocked by N(omega)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase), HOE 140 (Icatibant, a specific B2-kinin receptor antagonist), and dichloroisocoumarin (DCIC, a serine protease inhibitor that blocks local kinin formation). These results clearly show that there is a synergistic effect on NO formation when amlodipine is combined with ACE inhibition. Our data suggest that kinin-mediated coronary NO production may contribute importantly to the beneficial therapeutic action of ACE inhibitors, especially in combination with amlodipine in the treatment of heart disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10672850&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
The Effects of Amlodipine on Left Ventricular Mass and Diastolic Function in Concentric and Eccentric Left Ventricular Hypertrophy.

Fak AS, Okucu M, Tezcan H, Bodur G, Oktay A.

Department of Cardiology, Marmara University School of Medicine, Istanbul, Turkey

BACKGROUND: The effects of the antihypertensive therapy with amlodipine (5-10 mg/day) on left ventricular mass and diastolic function were examined in 30 mild to moderate essential hypertensive patients who have left ventricular hypertrophy (LVH) and diastolic dysfunction. METHODS AND RESULTS: Each patient's left ventricular mass was measured, and left ventricular diastolic function was assessed by echocardiographic Doppler examination at entry, and at 3 and 6 months after the initiation of the treatment. Amlodipine reduced both blood pressure (from 164 +/- 14/104 +/- 6 mmHg to 134 +/- 9/83 +/- 4 mmHg) and left ventricular mass index (from 160 +/- 30 g/m(2) to 137 +/- 26 g/m(2)) significantly at 3 months and both parameters maintained at these levels for 6 months. When the patients were classified according to the type of the LVH, a significant regression in left ventricular mass index was seen only in the patients who had concentric LVH was a relative wall thickness >/=0.44 (n = 16), but not in the eccentric LVH group (n = 14), although both groups were not significantly different from each other regarding the basal hemodynamic parameters, baseline left ventricular mass index and the decrease in blood pressure in response to amlodipine treatment. The mitral inflow E/A ratio did not show any significant change in either group. CONCLUSIONS: Amlodipine produced significant regression in LVH only in the patients with concentric LVH, but not those with eccentric LVH, while it did not change the diastolic dysfunction. Therefore, the type of LVH seems to be an important feature in determining the effects of antihypertensive treatment on left ventricular mass index.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10684405&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
Efficacy and Safety of Nifedipine Coat-Core versus Amlodipine in Patients With Mild to Moderate Essential Hypertension: Comparison of 24-Hour Mean Ambulatory Diastolic Blood Pressure.

Byyny RL, Shannon T, Schwartz LA, Rotolo C, Jungerwirth S.

Bayer Corporation Pharmaceutical Division, University of Colorado Health Sciences Center, Denver, Colorado, USA

BACKGROUND: Calcium channel blockers have been successfully used for the treatment of hypertension. In this study, the antihypertensive efficacy and safety of the dihydropyridine calcium channel blockers nifedipine coat-core 30 mg and amlodipine 5 mg were evaluated. METHODS: This multicenter, double-blind, prospective, randomized, parallel-arm study compared once daily administration of nifedipine coat-core 30 mg with once daily amlodipine 5 mg in subjects with mild-to-moderate essential hypertension. A 4-week placebo run-in period was followed by an 8-week active treatment period. Blood pressure reduction was measured by ambulatory blood pressure monitoring and casual office blood pressure measured by mercury sphygmomanometer. RESULTS: Nifedipine coat-core and amlodipine produced equivalent reductions in mean diastolic blood pressure, as determined by 24-hour ambulatory blood pressure monitoring. Mean reduction in diastolic blood pressure was 5.4 mmHg and 5.8 mmHg for nifedipine coat-core and amlodipine, respectively. Both drugs were well tolerated and neither treatment resulted in a significant change in heart rate. CONCLUSIONS: Nifedipine coat-core 30 mg once-daily is comparable to amlodipine 5 mg once-daily for blood pressure reduction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10684445&dopt=Abstract amlodipine Norvasc



amlodipine Norvasc
The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth.

James JA, Marley JJ, Jamal S, Campbell BA, Short CD, Johnson RW, Hull PS, Spratt H, Irwin CR, Boomer S, Maxwell AP, Linden GJ.

Turner Dental School, University of Manchester, UK.

BACKGROUND/AIMS: To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD: A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS: A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS: The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10703656&dopt=Abstract amlodipine Norvasc