Description
Nisoldipine D4 is another long-acting dihydropyridine calcium channel blocker effective in the treatment of hypertension and angina pectoris. It is reported to have little or no cardiodepressive activity and to be more effective than nifedipine in reducing blood pressure in hypertensives. Nisoldipine has also been shown to be effective in the management of congestive heart failure. Reduction in dosage is necessary in patients with hepatic, but not renal impairment.
Chemical Properties
Nisoldipine D4 is Light Tan Crystals
Originator
Bayer AG (Germany)
Uses
Dihydropyridine calcium channel blocker. Antihypertensive and antianginal
Uses
Labeled Nisoldipine, intended for use as an internal standard for the quantification of Nisoldipine by GC- or LC-mass spectrometry.
Definition
ChEBI: A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a methoxycarbonyl group at position 3, an o-nitrophenyl group at position 4, and an isobutoxycarbonyl group at position 5. The racemate,
calcium channel blocker, is used in the treatment of hypertension and angina pectoris.
Manufacturing Process
Boiling a solution of 12.7 g of 2'-nitrobenzylideneacetoacetic acid methyl ester
and 7.1 g of β-amino-crotonic acid isopropyl ester in 50 ml of methanol for 10
hours yielded 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5-
dicarboxylic acid 3-methyl ester-5-isopropyl ester of melting point 174°C
(from ethanol). Yield 48% of theory.
Brand name
Sular (Sciele);Baymycard.
Therapeutic Function
Coronary vasodilator
General Description
In vitro studies show that the effects ofnisoldipine, 1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylic acid methyl 2-methylpropyl ester(Sular), on contractile processes are selective, with greaterpotency on vascular smooth muscle than on cardiac muscle.
Nisoldipine is highly metabolized, with five majormetabolites identified. As with most of the dihydropyridines,the cytochrome P450 (CYP) 3A4 isozyme is mainlyresponsible for the metabolism of nisoldipine. The majorbiotransformation pathway appears to involve the hydroxylationof the isobutyl ester side chain. This particular metabolitehas approximately 10% of the activity of the parentcompound.
Biochem/physiol Actions
L-type (CaV1.2) calcium channel blocker; dihydropyridine-type calcium channel blocker with selectivity for smooth muscle (CaV1.2b) over cardiac muscle (CaV1.2a). Arterial vasodilator and antihypertensive agent.
References
[1] Patent: WO2004/2958, 2004, A1. Location in patent: Page 4-5
