Nicardipine

Absorption

While nicardipine is completely absorbed, it is subject to saturable first pass metabolism and the systemic bioavailability is about 35% following a 30 mg oral dose at steady state.

Toxicity

Oral LD50 Rat = 184 mg/kg, Oral LD50 Mouse = 322 mg/kg

Originator

Nicodel,Mitsui,Japan,1981

The Uses of Nicardipine

Nicardipine is a dihydropyridine calcium channel blocker. Antianginal; antihypertensive. Neuroprotective & Neuroresearch products.

The Uses of Nicardipine

Vasodilator.

The Uses of Nicardipine

It is used for arterial hypertension, chronic, stable angina pectoris, preventing angina pectoris, and for ischemic-type abnormalities of brain blood flow.

Background

A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [PubChem]

Indications

Used for the management of patients with chronic stable angina and for the treatment of hypertension.

Definition

ChEBI: Nicardipine is a racemate comprising equimolar amounts of (R)- and (S)-nicardipine. It is a calcium channel blocker which is used to treat hypertension. It has a role as an antihypertensive agent, a calcium channel blocker, a vasodilator agent and an autophagy inhibitor. It contains a (S)-nicardipine and a (R)-nicardipine.

Manufacturing Process

A mixture of 4.98 g of acetoacetic acid N-benzyl-N-methylaminoethyl ester, 2.3 g of β-aminocrotonic acid methyl ester, and 3 g of m-nitrobenzaldehyde was stirred for 6 hours at 100°C in an oil bath. The reaction mixture was subjected to a silica gel column chromatography (diameter 4 cm and height 25 cm) and then eluted with a 20:1 mixture of chloroform and acetone. The effluent containing the subject product was concentrated and checked by thin layer chromatography. The powdery product thus obtained was dissolved in acetone and after adjusting the solution with an ethanol solution saturated with hydrogen chloride to pH 1-2, the solution was concentrated to provide 2 g of 2,6-dimethyl-4-(3'-nitrophenyl)1,4-dihydropyridine-3,5-dicarboxylic acid 3-methylester-5-β-(N-benzyl-N-methylamino)ethyl ester hydrochloride. The product thus obtained was then crystallized from an acetone mixture, melting point 136°C to 140°C (decomposed).

brand name

Cardene(PDL Biopharma); Cardene (Roche).

Therapeutic Function

Vasodilator

Mechanism of action

Nicardipin relaxes smooth musculature of vessels, lowers resistance of coronary and peripheral vessels, increases blood flow in vessels of the brain, causes a moderate and stable hypotensive effect, and reduces the myocardial need for oxygen.

Pharmacokinetics

Nicardipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetal's variant angina. Nicardipine is similar to other peripheral vasodilators. Nicardipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

Synthesis

Nicardipine, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-methyl-2-[(methylphenylmethyl)- amino]ethyl ester 3,5-pirididincarboxylic acid (19.3.7), is synthesized in a manner analogous to the synthesis of nifedipine, the only difference being that in the Hantsch synthesis, two different |?-dicarbonyl compounds are used simultaneously with o-nitrobenzaldehyde. During this, one of these in the enamine form of acetoacetic ester is simultaneously used as an amine component. A heterocyclization reaction is accomplished by reacting, the methyl ester of |?-aminocrotonic acid with the 2-methyl-2-benzylaminoethyl ester of acetoacetic acid.

Metabolism

Nicardipine HCl is metabolized extensively by the liver.