Disease relevance of aranidipine

• We investigated the vasodilating action of MPC-1304, one of the most potent dihydropyridines causing hypotension, in anesthetized dogs and compared this with its binding properties [1].
• Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris [2].
• The decreases in proteinuria were observed in the aranidipine-treated group at weeks 6, 8, and 10, whereas in the M-1 group, significant reduction was attained only at week 6 [3].
• In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension [4].
• During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group [4].

High impact information on aranidipine

• Only MPC-1304 increased the renal blood flow [5].
• In WKY, MPC-1304 and nifedipine reduced the mean blood pressure and systemic vascular resistance to lesser degrees than in SHR [5].
• One possible mechanism for this difference in the effect on renal circulation between SHR and WKY may involve the potent antagonizing effects of MPC-1304 on alpha-2 adrenoceptor-mediated vasoconstriction [5].
• The purpose of this study was to compare the regional vascular effect of a novel dihydropyridine derivative, MPC-1304 [(+/-)- methyl-2-oxopropyl-1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylate], with that of nifedipine and manidipine in conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) [5].
• Contribution of aranidipine metabolites with slow binding kinetics to the vasodilating activity of aranidipine [6].

Chemical compound and disease context of aranidipine

• The effects of MPC-1304, a new calcium channel blocker, on blood pressure, serum lipoproteins, and carbohydrate metabolism were compared with those of atenolol in a group of patients with mild to moderate essential hypertension [7].
• This chronic ingestion of MPC-1304 and nicardipine inhibited the development of hypertension and reduced the concentration of blood urea nitrogen, creatinine, triglyceride and total cholesterol in serum [8].
• MPC-1304 ((+-)-methyl 2-oxopropyl 1,4-dihydro 2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, CAS 86780-90-7), a new calcium antagonist, was orally administered to 10 outpatients with mild essential hypertension [9].

Biological context of aranidipine

• MPC-1304 significantly reduced the renal blood flow without altering renal vascular resistance, in striking contrast to its renal effect in SHR [5].
• Receptor occupation and pharmacokinetics of MPC-1304, a new Ca2+ channel antagonist, in spontaneously hypertensive rats [10].
• At 1 and 6 h after oral administration of MPC-1304 (10 mg/kg) in SHR, there was significant decrease (48%) in the number of [3H](+)-PN 200-110 binding sites (Bmax) in myocardial membranes compared to control values [10].
• Both aranidipine and M-1 reduced blood pressure by a similar magnitude [3].
• MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats [4].

Anatomical context of aranidipine

• The main metabolic products of MPC-1304 also inhibited the Ca(2+)-induced contraction in the isolated vascular smooth muscles [11].
• In myocytes, aranidipine (10 nmol/l to 1 micromol/l) concentration-dependently decreased T-type and L-type Ca(2+) currents [12].
• In the sinoatrial node, 0.1 micromol/l aranidipine increased cycle length, and decreased +V(max) and the slope of the phase 4 depolarization [12].
• Effects of aranidipine, a novel calcium channel blocker, on mechanical responses of the isolated rat portal vein: comparison with typical calcium channel blockers and potassium channel openers [13].
• When infused into the renal artery in anesthetized dogs, aranidipine (0.03 microg/kg/min) induced sustained increases in urine volume and urinary excretion of sodium and of potassium [14].

Associations of aranidipine with other chemical compounds

• These results suggest that MPC-1304 has a great ability to inhibit pressor responses to norepinephrine and peripheral sympathetic stimulation after its oral administration, and that this effect of MPC-1304 is closely correlated with its potent antihypertensive activity [15].
• The purpose of this study was to investigate the renal effects of aranidipine, a novel calcium channel blocker of the dihydropyridine type, and its active metabolite in anesthetized dogs and conscious spontaneously hypertensive rats (SHRs) [14].
• MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits [2].
• The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG) [2].
• Nifedipine, nisoldipine and aranidipine competitively inhibited the CYP1A2 activity [16].

Gene context of aranidipine

• Inhibition extent of the CYP2E1 activity by nifedipine and aranidipine were weak [16].
• In conclusion, aranidipine and efonidipine have the ability to induce ABCA1 protein by distinct mechanisms; protein kinase A is involved in the aranidipine-induced ABCA1 upregulation [17].
• The aranidipine metabolite, M-1 (0.1 microg/kg/min), also caused diuresis and natriuresis almost equal to those of nifedipine [14].

Analytical, diagnostic and therapeutic context of aranidipine

• The in vivo specific binding of [3H](+)-PN 200-110 in particulate fractions of aorta of SHR was significantly reduced (74.8 and 37.9%, respectively) at 1 and 6 after oral administration of MPC-1304 (3 mg/kg), while the myocardial [3H](+)-PN 200-110 binding was decreased only at 1 h later [10].
• Determination of aranidipine and its active metabolite in human plasma by liquid chromatography/negative electrospray ionization tandem mass spectrometry [18].
• During norepinephrine-induced constriction, the addition of aranidipine dilated both afferent and efferent arterioles in a dose-dependent manner; at 10(-6) M, 83 +/- 6% and 90 +/- 6% reversal, respectively [3].
• The aim of this study was to assess the pharmacokinetics and subsequent pharmacodynamic interaction of MPC-1304, a dihydropyridine Ca2+ antagonist, with other drugs in animal experiments [19].
• The electrophysiological effects of MPC-1304, a novel calcium antagonist, were examined using the conventional microelectrode and whole-cell patch-clamp techniques in guinea-pig hearts [20].

References