Hazard
Human systemic effects.
Description
Amlodipine is a dihydropyridine L-type calcium channel blocker that selectively inhibits calcium influx in cardiac and vascular smooth muscle.
1 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.
2 Formulations containing amlodipine have been used in the treatment of hypertension.
Chemical Properties
Yellow Solid
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.
Uses
A dihydropyridine calcium channel blocker; activity resides mainly in the (-)-isomer.
Uses
anti-hypertensive;calcium channel blocker
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.
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
