Nicardipine hydrochloride

Description

Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A₁, A_2A, and A₃ receptors with K_i values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC₅₀ value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca²⁺ (EC₅₀ = 0.5 μM).

Chemical Properties

Yellow Solid

Uses

Dihydropyridine calcium channel blocker. Antianginal; antihypertensive

Uses

Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A1, A2A, and A3 receptors with Ki values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC50 value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca2+ (EC50 = 0.5 μM).

Uses

anesthetic (topical)

Definition

ChEBI: Nicardipine hydrochloride is a dihydropyridine. It has a role as a geroprotector.

brand name

Cardene(PDL Biopharma); Cardene (Roche).

General Description

Nicardipine hydrochloride,1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylicacid methyl 2-[methyl(phenylmethyl)amino]ethylester hydrochloride (Cardene), is a more potent vasodilator ofthe systemic, coronary, cerebral, and renal vasculature andhas been used in the treatment of mild, moderate, and severehypertension. The drug is also used in the management of stableangina.

Biochem/physiol Actions

Blocks L-type voltage-dependent calcium channels; antihypertensive.

Clinical Use

Calcium-channel blocker:
Prophylaxis and treatment of angina
Mild to moderate hypertension
Acute life-threatening hypertension and post operative hypertension (IV)

Safety Profile

Poison by ingestion, intravenous, and intraperitoneal routes. Moderately toxic by subcutaneous route. Human systemic effects: decreased urine volume or anuria. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx an

Drug interactions

Potentially hazardous interactions with other drugs
Aminophylline: possibly increases aminophylline concentration.
Anaesthetics: enhanced hypotensive effect.
Antibacterials: metabolism possibly accelerated by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin.
Antidepressants: enhanced hypotensive effect with MAOIs.
Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone.
Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; negative inotropic effect possibly increased with itraconazole.
Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post synaptic alpha-blockers.
Antivirals: concentration possibly increased by ritonavir; use telaprevir with caution.
Cardiac glycosides: digoxin concentration increased.
Ciclosporin: concentration of ciclosporin increased
Grapefruit juice: concentration increased - avoid.
Tacrolimus: may increase tacrolimus levels.
Theophylline: possibly increased theophylline concentration.

Metabolism

Nicardipine is subject to saturable first-pass metabolism. It is extensively metabolised in the liver and excreted in the urine and faeces, mainly as inactive metabolites.

References

1) Merck 14 6495 2) Hulubei et al. (2012), 4-Isoxazolyl-1,4-dihydropyridines exhibit binding at the multidrug-resistance transporter; Bioorg. Med. Chem., 20 6620