Disease relevance of Lercanidipine

• Losartan and lercanidipine attenuate low-density lipoprotein oxidation in patients with hypertension and type 2 diabetes mellitus: a randomized, prospective crossover study [1].
• Lercanidipine: a review of its use in hypertension [2].
• In lercanidipine-treated animals a significant and dose-dependent effect on intimal hyperplasia was observed [3].
• These results suggest a direct antiatherosclerotic effect of lercanidipine, independent of modulation of risk factors such as hypercholesterolemia and/or hypertension as demonstrated by the absence of stereoselectivity [3].
• Similar balanced pre- and postcapillary vasodilation may be an explanation for the lower incidence of vasodilatory edema seen clinically with lercanidipine [4].

High impact information on Lercanidipine

• Blood pressure response rates reached 69.6% on enalapril plus lercanidipine as compared with 53.6% on enalapril plus HCTZ (difference between treatments, P > 0.05) [5].
• Lercanidipine : a review of its efficacy in the management of hypertension [6].
• The percentage of patients with evidence of oedema on physical examination (33.3 versus 9.8%, P = 0.011) and with symptoms of leg swelling (63.9 versus 22%, P < 0.001) and leg heaviness (47.2 versus 12.2%, P < 0.001) was also greater with amlodipine compared with lercanidipine [7].
• Lercanidipine is well tolerated, with most treatment-emergent events related to vasodilation [6].
• No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine [8].

Chemical compound and disease context of Lercanidipine

• On the other hand, PD (7.5, 15 and 22.5 mg/kg)- and U69 (5 and 20 mg/kg)-induced hypothermia was unaffected by the pretreatment of either NIM or LER [9].
• This study evaluates the effects of lercanidipine antihypertensive treatment on glucose homeostasis in patients with type II diabetes mellitus with mild to moderate hypertension [10].
• The objective of this 8-week open-label study was to compare the tolerability of lercanidipine, a dihydropyridine calcium-channel antagonist (CA), with that of other CAs in the treatment of hypertension [11].
• In particular, edema was least frequent in the lercanidipine group (2.8%) compared with the lacidipine group (7.5%) and the nifedipine group (10.1%) [12].
• After a 2-week placebo run-in period, these 2 drugs were compared in a controlled parallel-group study lasting 3 months, involving 53 patients with mild-to-moderate essential hypertension (26 assigned to manidipine and 27 to lercanidipine) [13].

Biological context of Lercanidipine

• There was no clinically relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine, and the effect was superimposable on that of placebo [8].
• The method can be used to quantify lercanidipine in human plasma covering a variety of pharmacokinetic or bioequivalence studies [14].
• Lercanidipine had the lowest negative inotropic efficacy (1 micromol/L LER: 60.3% basal < AML: 79.1% basal < NIF: 92.4 basal) and potency (IC50 NIF: 3.5 nmol/L < AML: 48 nmol/L < Ler: 127 nmol/L) in right atrial trabeculae [15].
• Therefore, we demonstrate for the first time that lercanidipine consistently decreased MMP-9 activity and reduced oxidative stress in hypertensive patients, thus suggesting a mechanism probably involved in the pleotropic actions of lercanidipine [16].
• The cell growth inhibition induced by lercanidipine and its enantiomers was reversible [17].

Anatomical context of Lercanidipine

• Proliferation of smooth muscle cells, assessed by incorporation of BrdU into DNA, was reduced by about 50%, 70%, 85%, and 80% by lercanidipine (0.3, 1, and 3 mg kg(-1) week(-1)) and its (R)-enantiomer, respectively [3].
• The nonhypotensive dose of lercanidipine countered in part glomerular injury, narrowing of capsular space, and tubular degeneration, and decreased mesangial cell augmentation in SHR [18].
• Effect of the new calcium antagonist lercanidipine and its enantiomers on the migration and proliferation of arterial myocytes [17].
• In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages [19].
• The aim of this study was to evaluate blood plasma variations in oxygen FRs in hypertensive patients treated with lercanidipine, a drug acting on blood pressure and microcirculation [20].

Associations of Lercanidipine with other chemical compounds

• The primary study objective was to prove non-inferiority of lercanidipine add-on versus HCTZ add-on in reducing sitting diastolic blood pressure; response rates and tolerability data were also observed [5].
• NIM (1 mg/kg; i.p.) and LDP (0.3 mg/kg; i.p.) used in the study produced no tail-flick analgesia [21].
• This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine [22].
• The in vitro effects were investigated of the new dihydropyridine calcium antagonist (CA) lercanidipine and its enantiomers on arterial myocyte (smooth muscle cell; SMC) migration and proliferation as related to L-type calcium channel inhibition [17].
• A double-blind, double-dummy, randomised, multicentre study to compare the efficacy and tolerability of lercanidipine with losartan [23].

Gene context of Lercanidipine

• In addition, lercanidipine inhibited the release of metalloproteinases in the extracellular medium (50% and 95% inhibition at 10(-5) M for MMP-9 and MMP-2, respectively) [19].
• In addition, lercanidipine decreased activated MMP-9 in hypertensive patients without and with diabetes (95% CI, -19 to -47%, P = 0.047, and -80 to -96%, P = 0.010, respectively) [16].
• A simple, sensitive and rapid ultra-performance liquid chromatography/positive electrospray ionization tandem mass spectrometry (UPLC/ESI-MS/MS) method has been developed and validated for the determination of lercanidipine in human plasma [14].
• We examined whether lercanidipine produces antioxidant effects and reduces MMP-9 activity in hypertensive patients in a placebo-controlled, crossover, single-blinded design study including 18 healthy volunteers (control group), and 14 hypertensive patients without (N = 7) or with (N = 7) diabetes mellitus [16].
• To directly rule out the role of calcium channels in the antiatherosclerotic properties of lercanidipine, we examined the effect of the compounds on serum-stimulated calcium influx in SMC [17].

Analytical, diagnostic and therapeutic context of Lercanidipine

• Antihypertensive efficacy of lercanidipine at 2.5, 5 and 10 mg in mild to moderate essential hypertensives assessed by clinic and ambulatory blood pressure measurements. Multicenter Study Investigators [8].
• Administration of NIM and LDP (15 min prior) significantly potentiated the analgesia produced by three kappa-opioid receptor agonists [21].
• Ultra-performance liquid chromatography/tandem mass spectrometry method for the determination of lercanidipine in human plasma [14].
• A selective HPLC method for determination of lercanidipine in tablets [24].
• Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required [22].

References