Description
Amlodipine is a dihydropyridine L-type calcium channel blocker that selectively inhibits calcium influx in cardiac and vascular smooth muscle. Acting as a vasodilator, amlodipine reduces blood pressure by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance. It inhibits calcium-induced contractions in depolarized rat aorta with an IC
50 value of 1.9 nM, displaying a slow rate of association and dissociation in isolated vascular and cardiac tissues. Amlodipine also demonstrates actions independent of L-type calcium channel blockade by regulating membrane fluidity and cholesterol deposition, stimulating nitric oxide production, acting as an antioxidant, and regulating matrix deposition
in vitro and
in vivo. Formulations containing amlodipine have been used in the treatment of hypertension.
Chemical Properties
Yellow Solid
Uses
A dihydropyridine calcium channel blocker; activity resides mainly in the (-)-isomer.
Uses
anti-hypertensive;calcium channel blocker
Uses
A deuterated dihydropyridine calcium channel blocker.;Application of Labeled APIs: Labeled Amlodipine, intended for use as an internal standard for the quantification of Amlodipine by GC- or LC-mass spectrometry.
Definition
ChEBI: A fully substituted dialkyl 1,4-dihydropyridine-3,5-dicarboxylate derivative, which is used for the treatment of hypertension, chronic stable angina and confirmed or suspected vasospastic angina.
brand name
Norvasc (Pfizer).
General Description
Amlodipine, 2-[, for the treatment of hypertension. Amlodipineis also marketed as a combination therapy with atorvastatinunder the tradename Norvasc for the management of highcholesterol and high blood pressure.
Hazard
Human systemic effects.
Clinical Use
Calcium-channel blocker:
Hypertension
Angina prophylaxis
Safety Profile
Human systemic effects. Whenheated to decomposition it emits toxic vapors of NOx andCl
-.
Drug interactions
Potentially hazardous interactions with other drugs
Aminophylline and theophylline: possibly increased
aminophylline and theophylline concentration.
Anaesthetics: enhanced hypotensive effect.
Antibacterials: metabolism possibly inhibited by
clarithromycin, erythromycin and telithromycin.
Antidepressants: enhanced hypotensive effect with
MAOIs, concentration possibly reduced by St John’s
wort.
Antiepileptics: effects probably reduced by
phenobarbital and primidone.
Antifungals: negative inotropic effect possibly
increased with itraconazole.
Antihypertensives: enhanced hypotensive effect;
increased risk of first dose hypotensive effect of postsynaptic alpha-blockers.
Antivirals: concentration increased by telaprevir and
possibly by ritonavir - reduce dose of amlodipine.
Ciclosporin: ciclosporin concentration may be
increased by up to 40%.
Lipid lowering agents: possibly increased risk of
myopathy - do not exceed 20 mg of simvastatin.1 Tacrolimus: possibly increased tacrolimus levels.
Metabolism
Amlodipine is extensively metabolised by the liver to
inactive metabolites with 10% of the parent compound
and 60% of metabolites excreted in the urine.
References
1) Mason et al. (2003), Novel vascular biology of third-generation L-type calcium channel antagonists: ancillary actions of amlodipine; Arterioscler. Thromb. Vasc. Biol., 23 2155
2) Asano et al. (2003), A calcium channel blocker activates both ecto-5(‘)-nucleotidase and NO synthase in HUVEC; Biochem. Biophys. Res. Commun., 311 625
3) Yu et al. (2003), Amlodipine modulates THP-1 cell adhesion to vascular endothelium via inhibition of protein kinase C signal transduction; Hypertension, 42 329
4) Zhou et al. (2004), Inhibition of oxidative stress and improvement of endothelial function by amlodipine in angiotensin II-infused rats; Am. J. Hypertension, 17 167
5) Ueda et al. (1993), A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects; Br. J. Clin. Pharmacol., 36 561
