lacidipine and lercanidipine

Many 1,4-dihydropyridines (DHPs) possess redox properties. In this review DHPs are surveyed as protectors against oxidative stress (OS) and related disorders, considering the DHPs as specific group of potential antioxidants with bioprotective capacities. They have several peculiarities related to antioxidant activity (AOA). Several commercially available calcium antagonist, 1,4-DHP drugs, their metabolites, and calcium agonists were shown to express AOA. Synthesis, hydrogen donor properties, AOA, and methods and approaches used to reveal biological activities of various groups of 1,4-DHPs are presented. Examples of DHPs antioxidant activities and protective effects of DHPs against OS induced damage in low density lipoproteins (LDL), mitochondria, microsomes, isolated cells, and cell cultures are highlighted. Comparison of the AOA of different DHPs and other antioxidants is also given. According to the data presented, the DHPs might be considered as bellwether among synthetic compounds targeting OS and potential pharmacological model compounds targeting oxidative stress important for medicinal chemistry.

Topics: Amlodipine; Animals; Antioxidants; Azetidinecarboxylic Acid; Calcium Channel Blockers; Cattle; Dihydropyridines; Epithelial Cells; Humans; Hydrogen; Lipoproteins, LDL; Mice; Microsomes; Mitochondria; Niacinamide; Nifedipine; Nitrobenzenes; Oxidants; Oxidative Stress; Piperazines

Two key events in atherosclerotic plaque formation are the deposition of lipids in cells of the vascular wall, and migration and proliferation of arterial smooth muscle cells from the tunica intima toward the media. It has been shown that various calcium-channel antagonists may delay plaque formation in animal models. Among these, the new and highly lipophilic calcium antagonists, such as lacidipine and lercanidipine, display the most promising antiatherosclerotic activities. This paper will review and discuss these beneficial effects.

Topics: Arteriosclerosis; Calcium Channel Blockers; Cardiovascular System; Cell Division; Cell Movement; Dihydropyridines; Endothelium; Humans; Lipid Metabolism; Macrophages; Muscle, Smooth; Myocardium

This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). 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. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.

Topics: Aged; Aged, 80 and over; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Female; Humans; Hypertension; Male; Middle Aged; Supine Position; Treatment Outcome

Irrespective of their clinical relevance, side effects cannot be considered a negligible problem in antihypertensive therapy. The aim of this trial was to evaluate the tolerability profile of lercanidipine with that of two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensives.. In a multicenter, double-blind, parallel study 828 elderly (aged > or =60 years) hypertensives were randomized to lercanidipine 10 mg/day (n = 420), amlodipine 5 mg/day (n = 200), or lacidipine 2 mg/day (n = 208) (ratio 2:1:1). If blood pressure (BP) control was unsatisfactory (systolic BP/diastolic BP > or =140/90 mm Hg), the dose of the double-blind medication was doubled and, as a further step, enalapril or atenolol (plus diuretic, if needed) was added. Patients were treated for an average of 12 months.. Amlodipine patients had significantly (P <.001) higher rates of edema (19%) and of early study discontinuations due to edema (8.5%) compared with lercanidipine (9% and 2.1%) and lacidipine patients (4% and 1.4%). Similarly, edema-related symptoms (lower limb swelling and heaviness) occurred significantly (P <.01) more often with amlodipine (50% and 45%, respectively) than with lercanidipine (35% and 33%) and lacidipine (34% and 31%). Most edema cases occurred in the first 6 months, a between-treatment difference being evident since beginning of treatment. Other drug-related adverse events did not differ between treatments. Blood pressure was equally and effectively reduced in the three groups.. The two lipophilic dihydropyridine calcium antagonists, lercanidipine and lacidipine, have an antihypertensive effect comparable to that of amlodipine, but a better tolerability profile.

Topics: Aged; Amlodipine; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Drug Therapy, Combination; Edema; Female; Humans; Hypertension; Male; Peripheral Vascular Diseases; Treatment Outcome

Multiple studies have demonstrated dihydropyridine calcium-channel blocker (CCB) therapy to be appropriate for the treatment of hypertension, as is reflected in treatment guidelines such as the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in the United States and the 1999 World Health Organization-International Society of Hypertension report. As with any drug class, successful treatment with CCBs depends on good patient compliance, which often hinges on drug tolerability. The differing characteristics among the various generations of CCBs may contribute to some compounds demonstrating superior tolerability. To test this hypothesis, the COHORT trial (named for the large group of participants) was undertaken in 828 elderly hypertensive patients aged > or = 60 years. This trial investigated the possible differences in patient tolerability between the third-generation agent amlodipine and the latest-generation agents lercanidipine and lacidipine. The primary endpoint of the study was the percentage of patients reporting edema, the most common side effect associated with CCB therapy. The study results indicated that while all three treatments were similarly efficacious in lowering blood pressure, lercanidipine and lacidipine were much better tolerated than amlodipine whether they were used as single agents or as initial therapy combined with other antihypertensive drugs. These newest-generation dihydropyridine CCBs offer the potential to reduce side effects, improve patient compliance, and ultimately help patients reach target blood pressures as recommended by the aforementioned guidelines.

Topics: Amlodipine; Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Humans; Multicenter Studies as Topic; Randomized Controlled Trials as Topic

Lacidipine, a dihydropyridine-based calcium antagonist (DHP), has already been demonstrated to possess antioxidant activity and to reduce the intracellular production of reactive oxygen species (ROS). To verify if this effect is a peculiarity of this molecule, or belongs to other DHPs, the activity of lacidipine was compared with those of amlodipine, lercanidipine, nimodipine, and nifedipine. The DHPs were incorporated in bovine aortic endothelial cells (BAECs). Cu(2+)-oxidized LDL (ox-LDL, 5 microM) was incubated with BAECs for 5 min. 2',7'-Dichlorofluorescein (DCF) as expression of intracellular ROS production was measured by flow cytometry. Ox-LDL induced a strong increase in intracellular ROS formation (p<0.001) that was significantly reduced only with lacidipine and lercanidipine (p from <0.05 to <0.01); the effect of lacidipine, however, resulted in being much more evident than lercanidipine (p<0.01); amlodipine, nimodopine, and nifedipine had no effect on ROS formation. The lowest IC50s, i.e. the concentrations determining the 50% reduction of ROS, were obtained with lacidipine (p<0.01). The inhibitory effect of lacidipine on ox-LDL-induced ROS production in endothelial cells is a peculiarity of this molecule through its antioxidant activity.

Topics: Amlodipine; Animals; Antioxidants; Cattle; Cells, Cultured; Dihydropyridines; Endothelium, Vascular; Fluoresceins; Humans; Lipoproteins, LDL; Molecular Structure; Nifedipine; Nimodipine; Reactive Oxygen Species