Efonidipine hydrochloride monoethanolate

Clinical efficacy of efonidipine hydrochloride, a T-type calcium channel inhibitor, on sympathetic activities.[Pubmed:12547996]

Circ J. 2003 Feb;67(2):139-45.

Dihydropyridine Ca antagonists cause reflex tachycardia related to their hypotensive effects. Efonidipine hydrochloride has inhibitory effects on T-type Ca channels, even as it inhibits reflex tachycardia. In the present study, the influence of efonidipine hydrochloride on heart rate and autonomic nervous function was investigated. Using an electrocardiogram and a tonometric blood pressure measurement, autonomic nervous activity was evaluated using spectral analysis of heart rate/systolic blood pressure variability. Three protocols were used: (1) a single dose of efonidipine hydrochloride was administered orally to healthy subjects with resting heart rate values of 75 beats/min or more (high-HR group) and to healthy subjects with resting heart rate values less than 75 beats/min (low-HR group); (2) efonidipine hydrochloride was newly administered to untreated patients with essential hypertension, and autonomic nervous activity was investigated after a 4-week treatment period; and (3) patients with high heart rate values (>/=75 beats/min) who had been treated with a dihydropyridine L-type Ca channel inhibitor for 1 month or more were switched to efonidipine hydrochloride and any changes in autonomic nervous activity were investigated. In all protocols, administration of efonidipine hydrochloride decreased the heart rate in patients with a high heart rate, reduced sympathetic nervous activity, and enhanced parasympathetic nervous activity. In addition, myocardial scintigraphy with (123)I-metaiodobenzylguanidine showed significant improvement in the washout rate and H/M ratio of patients who were switched from other dihydropyridine Ca antagonists to efonidipine hydrochloride. Efonidipine hydrochloride inhibits increases in heart rate and has effects on the autonomic nervous system. It may be useful for treating hypertension and angina pectoris, and may also have a cardiac protective function.

Effects of efonidipine hydrochloride on heart rate and circulatory changes due to stress.[Pubmed:19172462]

Clin Exp Hypertens. 2009 Feb;31(1):83-91.

Efonidipine hydrochloride is a dual Ca channel blocker that inhibits T-type Ca channels, which are localized in the sinoatrial node and are involved in the pacemaker mechanism of the heart, as well as L-type Ca channels. In the present study, the effect of efonidipine hydrochloride in inhibiting an increase in heart rate along with changes in circulation during mental and physical stress was examined using normotensive volunteers. A mental arithmetic test caused significant increases in heart rate and blood pressure, which were significantly inhibited 3 hours after oral administration of 40 mg of efonidipine hydrochloride but not at 1 week after cessation of administration. In contrast, the plasma norepinephrine, epinephrine, renin activity, and aldosterone levels following the test were unchanged at both 3 hours and 1 week after administration of efonidipine hydrochloride. Physical stress in the form of cold by immersing one hand in ice water for 2 minutes induced similar increases in the heart rate and blood pressure, which were significantly reduced at 3 hours but not at 1 week after administration of efonidipine hydrochloride. The plasma levels of the humoral factors previously described following the physical stress were unchanged at either 3 hours or 1 week after administration of efonidipine hydrochloride. These results suggest that efonidipine hydrochloride inhibits increases in heart rate and blood pressure due to stress, presumably by blocking T-type Ca channels rather than by inhibiting the sympathetic nervous system. Therefore, efonidipine hydrochloride is expected to be a Ca antagonist that exhibits a strong cardioprotective effect.

Effects of efonidipine hydrochloride on renal arteriolar diameters in spontaneously hypertensive rats.[Pubmed:12452329]

Hypertens Res. 2002 Sep;25(5):751-5.

Efonidipine, a calcium antagonist, has been reported to dilate not only afferent but also efferent arterioles, thereby reducing glomerular hydrostatic pressure. We investigated the effect of chronic treatment with efonidipine or lisinopril on the afferent and efferent arteriolar diameters by the vascular cast technique. Four-week-old spontaneously hypertensive rats (SHR) were divided into three groups: untreated, efonidipine (25 mg/kg/day)-treated, and lisinopril (3 mg/kg/day)-treated. At 22 weeks of age, the renal vasculatures were fixed at the maximally dilated condition. The morphometrical measurements showed that the treatments with efonidipine and lisinopril caused structural alteration of the vasculature, resulting in significantly greater efferent arteriolar diameters than in untreated SHR. In addition, lisinopril-treated rats had wider afferent lumina. The renoprotective effect of efonidipine and lisinopril might be partly due to the structurally larger efferent arteriolar lumen.

Solid dispersions of efonidipine hydrochloride ethanolate with improved physicochemical and pharmacokinetic properties prepared with microwave treatment.[Pubmed:27553261]

Eur J Pharm Biopharm. 2016 Nov;108:25-31.

Drug absorption into the body is known to be greatly affected by the solubility of the drug itself. The active pharmaceutical ingredient efonidipine hydrochloride ethanolate (NZ-105) is a novel 1,4-dihydropyridine calcium antagonist that has a very low solubility in water. It is classified as a poorly soluble drug, and improvements in its solubility and higher bioavailability with oral administration are needed. In this study, employing microwave technology as a new means to improve solubility, we established a method for preparing solid dispersions using hydroxypropyl methylcellulose acetate succinate as a polymeric carrier and urea as a third component. This effective method has a treatment time of several minutes (simple) and does not require the use of organic solvents (low environmental impact). The third component, urea, acts to lower the melting point of NZ-105, which promotes amorphization. This greatly improves the solubility compared with the microwave-treated product of NZ-105/HPMC-AS binary system. The solid dispersion prepared with this method, in addition to evaluation in vitro, was tested in vivo using beagle dogs and shown to be effective from the eightfold improvement in absorption compared with NZ-105 alone based on the area under the curve.

Identification of R(-)-isomer of efonidipine as a selective blocker of T-type Ca2+ channels.[Pubmed:15545287]

Br J Pharmacol. 2004 Dec;143(8):1050-7.

Efonidipine, a derivative of dihydropyridine Ca(2+) antagonist, is known to block both L- and T-type Ca(2+) channels. It remains to be clarified, however, whether efonidipine affects other voltage-dependent Ca(2+) channel subtypes such as N-, P/Q- and R-types, and whether the optical isomers of efonidipine have different selectivities in blocking these Ca(2+) channels, including L- and T-types. To address these issues, the effects of efonidipine and its R(-)- and S(+)-isomers on these Ca(2+) channel subtypes were examined electrophysiologically in the expression systems using Xenopus oocytes and baby hamster kidney cells (BHK tk-ts13). Efonidipine, a mixture of R(-)- and S(+)-isomers, exerted blocking actions on L- and T-types, but no effects on N-, P/Q- and R-type Ca(2+) channels. The selective blocking actions on L- and T-type channels were reproduced by the S(+)-efonidipine isomer. By contrast, the R(-)-efonidipine isomer preferentially blocked T-type channels. The blocking actions of efonidipine and its enantiomers were dependent on holding potentials. These findings indicate that the R(-)-isomer of efonidipine is a specific blocker of the T-type Ca(2+) channel.

Inhibition of myocardial L- and T-type Ca2+ currents by efonidipine: possible mechanism for its chronotropic effect.[Pubmed:9671117]

Eur J Pharmacol. 1998 May 22;349(2-3):351-7.

Effects of efonidipine, a dihydropyridine phosphonate Ca2+ channel antagonist, on the guinea-pig heart were compared with those of nifedipine. In the sino-atrial node, 1 microM efonidipine produced increase in cycle length accompanied by prolongation of the phase 4 depolarization which was not prominent with 0.1 microM nifedipine. In ventricular myocytes, both efonidipine and nifedipine produced inhibition of the L-type Ca2+ current, nifedipine being tenfold more potent than efonidipine. Efonidipine also inhibited the T-type Ca2+ current at higher concentrations but nifedipine did not. Both Ca2+ channel antagonists had no or only a weak effect on K+ currents. In addition, 40 microM Ni2+, which selectively inhibited the T-type Ca2+ current, had no effect on myocardial Ca2+ transients and contractile force. In conclusion, efonidipine was shown to have inhibitory effects on both L- and T-type Ca2+ currents, which may contribute to its high negative chronotropic potency.

Efonidipine hydrochloride monoethanolate (NZ-105 hydrochloride monoethanolate) is a dual T-type and L-type calcium channel blocker (CCB).

Efonidipine hydrochloride monoethanolate,111011-76-8,Natural Products,Calcium Channel, buy Efonidipine hydrochloride monoethanolate , Efonidipine hydrochloride monoethanolate supplier , purchase Efonidipine hydrochloride monoethanolate , Efonidipine hydrochloride monoethanolate cost , Efonidipine hydrochloride monoethanolate manufacturer , order Efonidipine hydrochloride monoethanolate , high purity Efonidipine hydrochloride monoethanolate