General Description
Odorless yellow crystals or powder. Tasteless.
Reactivity Profile
NIFEDIPINE(21829-25-4) is sensitive to light.
Air & Water Reactions
Aqueous solutions are very sensitive to light. . Insoluble in water.
Fire Hazard
Flash point data for this chemical are not available; however, NIFEDIPINE is probably combustible.
Description
Nifedipine (21829-25-4) is a clinically useful L-type calcium blocker.
Originator
Adalat,Bayer,W. Germany,1975
Definition
ChEBI: Nifedipine is a dihydropyridine, a methyl ester and a C-nitro compound. It has a role as a calcium channel blocker, a vasodilator agent, a tocolytic agent and a human metabolite.
Manufacturing Process
45 grams 2-nitrobenzaldehyde, 80 cc acetoacetic acid methyl ester, 75 cc
methanol and 32 cc ammonia are heated under reflux for several hours,
filtered off, cooled and, after suction-filtration, 75 grams of yellow crystals of
MP 172° to 174°C are obtained, according to US Patent 3,485,847.
Brand name
Adalat (Bayer); Afeditab (Watson);Procardia (Pfizer).
Therapeutic Function
Coronary vasodilator
World Health Organization (WHO)
Nifedipine is a dihydropyridine calcium channel blocker. It is
listed in the WHO Model List of Essential Drugs. The 10mg tablet is retained on the
list for short-term treatment of hypertension. Sustained-release preparations are
advised for long-term treatment.
Biological Activity
L-type calcium channel blocker.
Biochem/physiol Actions
Nifedipine is a L-type Ca2+ channel blocker; and induces apoptosis in human glioblastoma cells. Nifedipine has neuroprotection activity and protects substantia nigra. Nifedipine has antioxidant potential. Nifedipine downregulates inflammatory cytokines like macrophage inflammatory protein-2 (MIP-2), tumor necrosis factor-α (TNF-α). Nifedipine has antihypertensive properties. Nifedipine inhibits extracellular region of adenosine A2a receptor (ADORA2A) gene.
Mechanism of action
Nifedipin causes relaxation of smooth musculature, dilation of coronary and peripheral
arteries, and reduction of peripheral resistance and arterial blood pressure, and enhances
oxygen supply to the heart.
Clinical Use
The prototype of this class, nifedipine, has potent peripheralvasodilatory properties. It inhibits the voltage-dependentcalcium channel in the vascular smooth muscle but has littleor no direct depressant effect on the SA or AV nodes, eventhough it inhibits calcium current in normal and isolated cardiactissues. Nifedipine is more effective in patients whoseanginal episodes are caused by coronary vasospasm and isused in the treatment of vasospastic angina as well as classicangina pectoris. Because of its strong vasodilatory properties,it is used in selected patients to treat hypertension.
Synthesis
Nifedipine, dimethyl ether 1,4-dihydro-2,6-dimethyl-4-(2??-nitrophenyl)-3,5-
piridindicarboxylic acid (19.3.16), is synthesized by a Hantsch synthesis from two
molecules of a |?-dicarbonyl compound?amethyl acetoacetate, using as the aldehyde component?a
2-nitrobenzaldehyde and ammonia. The sequence of the intermediate stages of
synthesis has not been completely established.
Drug interactions
Potentially hazardous interactions with other drugs
Aminophylline: possibly increases aminophylline
concentration.
Anaesthetics: enhanced hypotensive effect.
Anti-arrhythmics: concentration of dronedarone
increased.
Antibacterials: metabolism accelerated by rifampicin;
metabolism possibly inhibited by clarithromycin,
erythromycin and telithromycin.
Antidepressants: metabolism possibly inhibited by
fluoxetine; concentration reduced by St John’s wort;
enhanced hypotensive effect with MAOIs.
Antiepileptics: effect reduced by carbamazepine,
barbiturates, phenytoin and primidone.
Antifungals: metabolism possibly inhibited by
itraconazole and ketoconazole; concentration
increased by micafungin; negative inotropic effect
possibly increased with itraconazole.
Antihypertensives: enhanced hypotensive effect,
increased risk of first dose hypotensive effect of
post-synaptic alpha-blockers; occasionally severe
hypotension and heart failure with beta-blockers.
Antivirals: concentration possibly increased by
ritonavir; use telaprevir with caution.
Cardiac glycosides: digoxin concentration possibly
increased.
Ciclosporin: may increase ciclosporin level, but not a
problem in practice; nifedipine concentration may be
increased.
Cytotoxics: metabolism of vincristine possibly
reduced.
Grapefruit juice: concentration increased - avoid.
Magnesium salts: profound hypotension with IV
magnesium.
Tacrolimus: increased tacro
Metabolism
Nifedipine is metabolised in the gut wall and oxidised in
the liver via the cytochrome P450 isoenzyme CYP3A4, to
inactive metabolites.
Excreted mainly as metabolites via the kidney
References
1) Vater et al., (1972), (Pharmacology of 4-(2′-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (Nifedipine, BAY a 1040); Arzneimittelforschung, 22 1
