Disease relevance of Franidipine

• Diabetic patients and very elderly patients with mild-to-moderate hypertension also respond favourably to treatment with manidipine [1].
• Manidipine is also effective in hypertensive patients with comorbidities, such as type 2 diabetes mellitus and/or renal impairment, and appears to improve insulin sensitivity without affecting metabolic function [2].
• Unlike older-generation DHPs, which preferentially act on L-type channels, manidipine has been shown to have beneficial effects on intrarenal haemodynamics, proteinuria and other measures of renal functional decline in the first clinical trials involving hypertensive patients with chronic renal failure [3].
• Male SHRs underwent uninephrectomy at age 10 to 11 weeks and were subsequently assigned to no treatment (control), a predetermined subvasodepressor (low) dose of manidipine (2.5 mg/kg body weight), or a predetermined antihypertensive (high) dose of manidipine (20 mg/kg body weight) [4].
• Temporary symptom worsening caused by manidipine hydrochloride in two patients with Parkinson's disease [5].

Psychiatry related information on Franidipine

• These results suggest that antihypertensive therapy with manidipine may be beneficial in maintaining RBF during emotional stress [6].

High impact information on Franidipine

• Nanomolar concentrations of the five Ca2+ channel blockers amlodipine, felodipine, manidipine, verapamil, or diltiazem significantly decreased both the constitutive and platelet-derived growth factor BB-dependent collagen deposition in the ECM formed by human vascular smooth muscle cells and fibroblasts [7].
• We conclude that manidipine, at nanomolar concentrations, is efficacious in modulating gene transcriptions that are involved in proinflammatory changes of mesangial cells [8].
• Additionally, the induction of c-fos, c-jun, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase transcription was inhibited by manidipine [8].
• Thus, manidipine, at pharmacological concentrations that are one to two orders of magnitude lower than those required for inhibition of agonist- or depolarization (K+)-induced vasoconstriction, causes changes in the activity of the genes that code for inflammatory mediators [8].
• Treatment of 5/6-nephrectomized rats with TCV-116 or manidipine significantly decreased glomerular expression of alpha-smooth muscle actin and desmin, thereby indicating that these drugs prevented glomerular phenotypic changes in 5/6-nephrectomized rats [9].

Chemical compound and disease context of Franidipine

• Delapril/manidipine 30 mg/10 mg is a new oral, once-daily, fixed combination of an ACE inhibitor and a dihydropyridine calcium-channel antagonist for the treatment of essential hypertension [10].
• We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension [11].
• METHODS: This multicenter, double-blind trial compared manidipine and enalapril in patients with type 2 diabetes and hypertension (diastolic blood pressure [DBP] 90-104 mm Hg, systolic blood pressure [SBP] < or =190 mm Hg) [12].
• These findings suggest that hANP and ET levels are systematically changed by manidipine chloride in patients with essential hypertension [13].
• Safety profile favored manidipine, which was associated with significantly less ankle edema than was amlodipine [14].

Biological context of Franidipine

• Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg [15].
• In a dose-finding study in 400 patients with mild to moderate hypertension, delapril/manidipine 30mg/10mg once daily produced the greatest reduction in blood pressure (BP) of the combinations tested [10].
• Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation [16].
• The IC50 of CV-4093 obtained for the K outward current was 3000 times larger than that obtained for the Ca inward current [17].
• In SHR, MPC-1304 at a dose of 1 mg/kg reduced the mean blood pressure and systemic vascular resistance and increased cardiac output, as did nifedipine (10 mg/kg) and manidipine (3 mg/kg) [18].

Anatomical context of Franidipine

• If these results are confirmed, calcium channel antagonists that activate the sympathetic nervous system to a lesser extent, such as manidipine, may become first-choice calcium channel antagonists because of their more favourable adverse event profile [19].
• Effects of CV-4093, a newly synthesized dihydropiridine type of Ca antagonist, on membrane currents in enzymatically dispersed single smooth muscle cells of the rabbit main pulmonary artery were investigated using the single electrode voltage clamp method [17].
• CV-4093 apparently has highly selective and long-lasting inhibitory actions on the Ca current in smooth muscle cells of the rabbit main pulmonary artery [17].
• In small coronary and renal arteries maximally activated with KCl solution, nifedipine and manidipine concentrations dependently inhibited the calcium concentration response curves [20].
• Nisoldipine was the most potent and CV-4093 was the least potent among these drugs in terms of negative inotropic effect in normally polarized papillary muscles and negative chronotropic effect in right atria of guinea pigs [21].

Associations of Franidipine with other chemical compounds

• Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment [15].
• Effects of manidipine, a dihydropyridine derivative, on L-type Ca2+ currents were examined in guinea-pig ventricular cells, using the whole-cell patch-clamp method [22].
• We also observed a statistically significant negative correlation between the change in systolic blood pressure caused by manidipine chloride and the change in hANP levels before and after treatment [13].
• Determination of manidipine and its pyridine metabolite in human serum by high-performance liquid chromatography with ultraviolet detection and column switching [23].
• These unexpected vasorelaxant actions of ET-1 in the presence of manidipine were likely caused by the dual effects of antagonism of its own intrinsic vasoconstrictor action (through calcium channel blockade), as well as ET-1-evoked release of the endothelium-derived relaxing factor, nitric oxide [24].

Gene context of Franidipine

• These observations showed that amlodipine and manidipine reduced superoxide generation by the inhibition of the overexpression of NADPH oxidase in Ang II-stimulated endothelial cells [25].
• Conclusion These results indicate that the stereoselective disposition of manidipine was altered by GFJ, as an inhibitor of CYP3A4 [26].
• In conclusion, manidipine decreases p22(phox) and increases HO-1 mRNA production and protein level [27].
• Effect of manidipine on gene expression and protein level of oxidative stress-related proteins: p22phox and HO-1: relevance for antihypertensive and anti-remodeling effects [27].
• AT1 receptor mRNA content in the adrenal gland was significantly (p < 0.01) decreased by treatment with manidipine or delapril [28].

Analytical, diagnostic and therapeutic context of Franidipine

• The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group [16].
• A stereoselective and highly sensitive method using chiral chromatography and successive column-switching liquid chromatography is described for the determination of manidipine enantiomers in human serum [29].
• Oral administration of manidipine 10 mg before induction of anaesthesia is a simple and effective method for attenuating pressor response to laryngoscopy and tracheal intubation [30].
• Manidipine reduced the filtration fraction from 0.260 to 0.243, suggesting a preferential reduction in efferent arteriolar resistance [31].
• We conducted a placebo-controlled, randomized, and double-blinded study to evaluate the efficacy of manidipine given orally in attenuating the cardiovascular responses to laryngoscopy and tracheal intubation [30].

References