Chemical Properties
White Crystalline Solid
Uses
A dihydropyridine calcium channel blocker. Used as an antianginal and antihypertensive
Uses
Amlodipine besylate is a L-type calcium channel blocker which may be used for the treatment of angina pectoris and hypertension. Amlodipine also inhibits growth of human epidermoid carcinoma A431 cells and has antireproductive effects in male rats.
Uses
Angiotensin II inhibitor prodrug, antihypertensive
Definition
ChEBI: The benzenesulfonate salt of amlodipine.
Manufacturing Process
2-[(2-Aminoethoxy)methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-
methoxycarbonyl-6-methyl-1,4-dihydropyridine (amlodipine) was prepared
from 2-(phthalimidoaminoethoxy)acetoacetate, 2-chlorobenzaldehyde and
methyl-3-aminocrotonate under refluxing in ethanol for 24 hours. The
ketoester was prepared by the method of Troostwijk and Kellog (JCS Chem.
Comm., 1977, p.932). Methyl-3-aminocrotonate can be prepared by known
method. Phthalimido-amino-protecting group was removed using hydrazine
hydrate in ethanol at the reflux temperature.
Although amlodipine is effective as the free base, in practice it is best
administered form of a salt of a pharmaceutically acceptable acid.
Benzensulphonic salt of amlodipine was prepared as follows: Amlodipine base
(65.6 g, 0.161 mols) was slurried in industrial methylated spirit (denatured
alcohol, 326.4 ml) and cooled to 5°C. Benzensulphonic acid (26.2 g, 0.168
mols) was dissolved in industrial methylated spirit (65.6 ml) at 5°C and added
to base. The resulting slurry was then granulated, filtered and washed with 2
volumes the same solvent (65.6 ml). The damp solid was slurred at 5°C for 1
hr in 327.6 ml industrial methylated spirit, filtered, washed with 2 volumes of
the same solvent (65.6 ml) and dried under vacuum at 55°C for 24 hr. A yield
of besylate salt of amlodipine 65 g.
Brand name
Norvasc (Pfizer);Istin.
Therapeutic Function
Antianginal, Antihypertensive
General Description
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Amlodipine besylate is a calcium channel blocker, which inhibits the trans membrane influx of calcium ions into vascular smooth muscles and cardiac muscle. It belongs to the dihydropyridine family. It is used in combination with atorvastatin calcium to treat vasospastic angina, chronic stable angina, hypertension, in elevated serum triglyceride levels, primary dysbetalipoproteinemia.
Biological Activity
L-type calcium channel blocker that displays antihypertensive properties. Inhibits Ca 2+ -induced contractions in depolarized rat aorta (IC 50 = 1.9 nM) and displays vasoprotective effects in cardiovascular disease. Inhibits proliferation of human vascular smooth muscle cells and epidermoid carcinoma A431 cells (IC 50 = 25 μ M).
Biochem/physiol Actions
Amlodipine is an L-type calcium channel blocker. Amlodipine belongs to a class of cardiovascular drugs, which act at the voltage gated calcium channel of the CaV1, or L-type, class. Amlodipine also has antihypertensive and antianginal effects. Its activity resides mainly in the (-)-isomer. Amlodipine inhibits growth of human epidermoid carcinoma A431 cells and has antireproductive effects in male rats.
Veterinary Drugs and Treatments
Oral amlodipine appears to be a useful agent in the treatment of
hypertension in cats and many consider it the drug of choice for this
indication. In pharmacokinetic studies, amlodipine has decreased
blood pressure in dogs with chronic renal disease, but its efficacy in
treating
hypertensive dogs has been disappointing.
Hypertension in cats is usually secondary to other diseases (often
renal failure or cardiac causes such as thyrotoxic cardiomyopathy or
primary hypertrophic cardiomyopathy, etc.) and is most often seen
in middle-aged or geriatric cats. These animals often present with
acute clinical signs such as blindness, seizures, collapse or paresis. A
cat is generally considered hypertensive if systolic blood pressure is
>160 mmHg. Early reports indicate that if antihypertensive therapy
is begun acutely, some vision may be restored in about 50% of cases
of blindness secondary to hypertension.
