|Drug class||ACE inhibitor|
|Main uses||High blood pressure, heart failure, diabetic kidney disease|
|Side effects||Cough, dizziness, tiredness, rash, muscle pain|
|Onset of action||With an hour|
|Duration of action||About a day|
|Typical dose||7.5 to 30 mg/day|
|Metabolism||Liver (active metabolite, moexiprilat)|
|Elimination half-life||1 hour; 2-9 hours (active metabolite)|
|Excretion||50% (faeces), 13% (urine)|
|Chemical and physical data|
|Molar mass||498.576 g·mol−1|
Moexipril, sold under the brand name Univasc among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can be given alone or with other medications. It is taken by mouth. Effects begin within an hour and last about a day.
Common side effects include cough, dizziness, tiredness, rash, and muscle pain. Other side effects may include angioedema, high potassium, low blood pressure, and kidney problems. Use in pregnancy may harm the baby. It is an angiotensin converting enzyme inhibitor (ACE inhibitor).
Moexipril was patented in 1980 and approved for medical use in 1995. It is available as a generic medication. In the United States 3 months of 15 mg per day costs about 33 USD. It appears to work less well in Black people.
It is generally taken at a dose of 7.5 to 30 mg per day.
Moexipril is generally well tolerated in elderly patients with hypertension. Hypotension, dizziness, increased cough, diarrhea, flu syndrome, fatigue, and flushing have been found to affect less than 6% of patients who were prescribed moexipril.
Mechanism of action
As an ACE inhibitor, moexipril causes a decrease in ACE. This blocks the conversion of angiotensin I to angiotensin II. Blockage of angiotensin II limits hypertension within the vasculature. Additionally, moexipril has been found to possess cardioprotective properties. Rats given moexipril one week prior to induction of myocardial infarction, displayed decreased infarct size. The cardioprotective effects of ACE inhibitors are mediated through a combination of angiotensin II inhibition and bradykinin proliferation. Increased levels of bradykinin stimulate in the production of prostaglandin E2 and nitric oxide, which cause vasodilation and continue to exert antiproliferative effects. Inhibition of angiotensin II by moexipril decreases remodeling effects on the cardiovascular system. Indirectly, angiotensin II stimulates of the production of endothelin 1 and 3 (ET1, ET3) and the transforming growth factor beta-1 (TGF-β1), all of which have tissue proliferative effects that are blocked by the actions of moexipril. The antiproliferative effects of moexipril have also been demonstrated by in vitro studies where moexipril inhibits the estrogen-stimulated growth of neonatal cardiac fibroblasts in rats. Other ACE inhibitors have also been found to produce these actions, as well.
Moexipril is available as a prodrug moexipril hydrochloride, and is metabolized in the liver to form the pharmacologically active compound moexiprilat. Formation of moexiprilat is caused by hydrolysis of an ethyl ester group. Moexipril is incompletely absorbed after oral administration, and its bioavailability is low. The long pharmacokinetic half-life and persistent ACE inhibition of moexipril allows once-daily administration.
Moexipril is highly lipophilic, and is in the same hydrophobic range as quinapril, benazepril, and ramipril. Lipophilic ACE inhibitors are able to penetrate membranes more readily, thus tissue ACE may be a target in addition to plasma ACE. A significant reduction in tissue ACE (lung, myocardium, aorta, and kidney) activity has been shown after moexipril use.
The synthesis of the all-important dipeptide-like side chain involves alkylation of the tert-butyl ester of L-alanine (2) with ethyl 2-bromo-4-phenylbutanoate (1); the presominane of the desired isomer is attributable to asymmetric induction from the adjacent chiral center. Reaction of the product with hydrogen chloride then cleaves the tert-butyl group to give the half acid (3). Coupling of that acid to the secondary amine on tetrahydroisoquinoline (4) gives the corresponding amine. The tert-butyl ester in this product is again cleaved with hydrogen chloride to afford moexipril (5).
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