Disease relevance of Mepirodipine

• These findings suggest that barnidipine can be used safely in patients with isolated clinic ("white coat") hypertension and in those with dipping patterns of circadian BP variation whose nocturnal BP is low before treatment [1].
• 5. These results indicate that barnidipine produces a sustained hypotension without affecting atrioventricular conduction time and plasma aldosterone concentration in conscious squirrel monkeys [2].
• The authors conducted the present pilot study to evaluate the possible effects of barnidipine on parameters involved in atherogenesis, oxidative stress, and clotting activity [3].

High impact information on Mepirodipine

• In the cerebral cortex of these rats, there was a significant (34%) decrease in Bmax values for (+)-[3H]PN 200-110 binding only at 0.5 hr after mepirodipine administration [4].
• At 0.5, 3 and 6 hr after an oral administration of mepirodipine (3 mg/kg) in SHR, there was a significant (69, 51 and 41%, respectively) decrease in the number of cardiac (+)-[3H]PN 200-110 binding sites (Bmax) compared to control values [4].
• The aim of the present study was to examine whether barnidipine increased renal blood flow in a conscious animal model for essential hypertension [5].
• Preferential renal and mesenteric vasodilation induced by barnidipine and amlodipine in spontaneously hypertensive rats [5].
• It was also clarified that nicardipine, benidipine, manidipine, and barnidipine were strong inhibitors of P-gp as well as CYP3A4 [6].

Chemical compound and disease context of Mepirodipine

• In the present study, a modified release product of a therapeutic drug for hypertension, Barnidipine hydrochloride, was developed [7].
• Four multicentre trials have investigated the efficacy and tolerability of treatment with once-daily, modified-release capsules of barnidipine, a long-acting dihydropyridine calcium antagonist, in patients with mild to moderate essential hypertension [8].
• Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients [9].
• Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension [10].
• The objective of this study was to compare the long-term efficacy and safety of 6 months' treatment with barnidipine and hydrochlorothiazide (HCTZ) as monotherapy in patients aged > or = 75 years with mild to moderate essential hypertension [11].

Biological context of Mepirodipine

• Evaluation of the antihypertensive effect of barnidipine, a dihydropyridine calcium entry blocker, as determined by the ambulatory blood pressure level averaged for 24 h, daytime, and nighttime. Barnidipine Study Group [1].
• Mepirodipine 3 x 10(-9) M significantly decreased the action potential amplitude and the maximum rate of depolarization [12].
• Efficiency of myocardial performance (work in relation to oxygen consumption) was low in postischemic controls (8% of total energy equivalents), but significantly improved in treated hearts, especially by barnidipine (15% efficiency) [13].
• The effects of mepirodipine, a new 1,4-dihydropyridine calcium antagonist, on the membrane potentials were examined on spontaneously beating rabbit sino-atrial (SA) node cells and on the membrane currents under voltage-clamped conditions [12].
• Heart rate in both sitting and standing positions was not affected by barnidipine [14].

Anatomical context of Mepirodipine

• Comparative effects of a new calcium channel antagonist, mepirodipine, on rabbit spontaneously beating sino-atrial node cells [12].
• Voltage-dependent effects of barnidipine in rat vascular smooth muscle [15].
• In the papillary muscle preparation, the dose causing a 50% decrease in developed tension was 44, 6.5 and 54 micrograms for mepirodipine, nifedipine and nicardipine, respectively [16].
• 2. In anaesthetized dogs, barnidipine (0.3-3 mu g/kg i.v.) dose-dependently decreased blood pressure and increased or preserved blood flow in the vertebral, coronary, femoral and renal arteries [17].
• Ca antagonistic properties of mepirodipine hydrochloride [+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl methyl 2,6-dimethyl-4- (m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride, YM-09730-5) were assessed by studying the pharmacological actions and binding characteristics of the drug in the stem coronary artery [18].

Associations of Mepirodipine with other chemical compounds

• 1. The metabolism and pharmacokinetics of barnidipine hydrochloride, a 1, 4-dihydropyridine calcium antagonist were evaluated following single oral administration of a sustained release formulation (SR) capsule comprising of quick and slow release pellets to healthy male volunteers [19].
• The plasma levels of ANP tended to increase, but those of aldosterone did not change with barnidipine [20].
• The mean +/- SD reductions in systolic and diastolic blood pressure were 19.2 +/- 13.6 and 14.4 +/- 7.0 mmHg, respectively, for barnidipine treatment, and 20.3 +/- 11.3 and 14.7 +/- 7.7 mmHg, respectively, for felodipine treatment [21].
• The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment [10].
• The incidence of drug-related adverse events was greater in the barnidipine than HCTZ-treated group but they were consistent with vasodilation and were categorised as mild to moderate [11].

Gene context of Mepirodipine

• Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR [22].
• We investigated the effect of barnidipine hydrochloride, a Ca(2+) channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction [22].
• Barnidipine significantly reduced the nighttime ambulatory SBP only in group 2 and the nighttime ambulatory DBP in groups 2 and 4 [1].
• Examination of metabolic pathways and identification of human liver cytochrome P450 isozymes responsible for the metabolism of barnidipine, a calcium channel blocker [23].
• 4. Barnidipine (1 and 3 mg/kg p.o.) increased plasma renin activity dose-dependently [2].

Analytical, diagnostic and therapeutic context of Mepirodipine

• Determination of a novel calcium channel antagonist, mepirodipine, in plasma by radioreceptor assay using (+)-[3H]PN 200-110 [24].
• Barnidipine, a novel calcium antagonist for once-daily treatment of hypertension: a multicenter, double-blind, placebo-controlled, dose-ranging study. Dutch Barnidipine Multicenter Study Group [14].
• These patients were given 6-week regimens of both barnidipine (20 mg) and placebo, preceding 24-h ambulatory blood pressure monitoring [8].
• The suitability of barnidipine for once-daily dosing was confirmed in a randomized, double-blind, placebo-controlled, crossover study of 20 patients [8].
• Determination of barnidipine in human serum and dog plasma by HPLC with electrochemical detection [25].

References