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Identification
Name Moexipril
Accession Number DB00691 (APRD01120)
Type small molecule
Groups approved
Description

Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Moexipril HCl
Moexipril hydrochloride
Moexiprilum [INN-Latin]
Salts Not Available
Brand names
Name Company
Univasc Schwarz
Brand mixtures
Brand Name Ingredients
Uniretic moexipril + hydrochlorothiazide
Categories
  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors
CAS number 103775-10-6
Weight Average: 498.5681
Monoisotopic: 498.236601452
Chemical Formula C27H34N2O7
InChI Key InChIKey=UWWDHYUMIORJTA-HSQYWUDLSA-N
InChI
InChI=1S/C27H34N2O7/c1-5-36-27(33)21(12-11-18-9-7-6-8-10-18)28-17(2)25(30)29-16-20-15-24(35-4)23(34-3)14-19(20)13-22(29)26(31)32/h6-10,14-15,17,21-22,28H,5,11-13,16H2,1-4H3,(H,31,32)/t17-,21-,22-/m0/s1
Plain Text
IUPAC Name
(3S)-2-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CC2=CC(OC)=C(OC)C=C2C[C@H]1C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropylamines
  • (Iso)quinolines and Derivatives
  • Amphetamines
  • Catecholamines and Derivatives
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Phenols and Derivatives
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • (Iso)quinolines and Derivatives
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
Pharmacology
Indication For the treatment of hypertension.
Pharmacodynamics Moexipril is a non-sulfhydryl containing precursor of the active angiotensin-converting enzyme (ACE) inhibitor moexiprilat. It is used to treat high blood pressure (hypertension). It works by relaxing blood vessels, causing them to widen. Lowering high blood pressure helps prevent strokes, heart attacks and kidney problems.
Mechanism of action Moexipril is a prodrug for moexiprilat, which inhibits ACE in humans and animals. The mechanism through which moexiprilat lowers blood pressure is believed to be primarily inhibition of ACE activity. ACE is a peptidyl dipeptidase that catalyzes the conversion of the inactive decapeptide angiotensin I to the vasoconstrictor substance angiotensin II. Angiotensin II is a potent peripheral vasoconstrictor that also stimulates aldosterone secretion by the adrenal cortex and provides negative feedback on renin secretion. ACE is identical to kininase II, an enzyme that degrades bradykinin, an endothelium-dependent vasodilator. Moexiprilat is about 1000 times as potent as moexipril in inhibiting ACE and kininase II. Inhibition of ACE results in decreased angiotensin II formation, leading to decreased vasoconstriction, increased plasma renin activity, and decreased aldosterone secretion. The latter results in diuresis and natriuresis and a small increase in serum potassium concentration (mean increases of about 0.25 mEq/L were seen when moexipril was used alone). Whether increased levels of bradykinin, a potent vasodepressor peptide, play a role in the therapeutic effects of moexipril remains to be elucidated. Although the principal mechanism of moexipril in blood pressure reduction is believed to be through the renin-angiotensin-aldosterone system, ACE inhibitors have some effect on blood pressure even in apparent low-renin hypertension.
Absorption Moexipril is incompletely absorbed, with bioavailability as moexiprilat of about 13% compared to intravenous (I.V.) moexipril (both measuring the metabolite moexiprilat), and is markedly affected by food, which reduces Cmax and AUC by about 70% and 40%, respectively, after the ingestion of a low-fat breakfast or by 80% and 50%, respectively, after the ingestion of a high-fat breakfast.
Volume of distribution
  • 183 L
Protein binding Moexiprilat is approxomately 50% protein bound.
Metabolism Rapidly converted to moexiprilat, the active metabolite. Conversion to the active metabolite is thought to require carboxyesterases and is likely to occur in organs or tissues, other than the gastrointestinal tract, in which carboxyesterases occur. The liver is thought to be one site of conversion, but not the primary site.
Route of elimination Moexiprilat undergoes renal elimination.
Half life Moexipril elimination half-life is approximately 1 hour. Moexiprilat elimination half-life is 2 to 9 hours.
Clearance
  • 441 mL/min
Toxicity Human overdoses of moexipril have not been reported. In case reports of overdoses with other ACE inhibitors, hypotension has been the principal adverse effect noted. Single oral doses of 2 g/kg moexipril were associated with significant lethality in mice. Rats, however, tolerated single oral doses of up to 3 g/kg. Common adverse effects include cough, dizziness, diarrhea, flu syndrome, fatigue, pharyngitis, flushing, rash, and myalgia
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00151 Moexipril Pathway SMP00151
Pharmacoeconomics
Manufacturers
  • Apotex inc
  • Glenmark generics ltd
  • Paddock laboratories inc
  • Teva pharmaceuticals usa inc
  • Schwarz pharma inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral 15 mg
Tablet, film coated Oral 7.5 mg
Prices
Unit description Cost Unit
Univasc 15 mg tablet 2.44 USD tablet
Univasc 7.5 mg tablet 2.13 USD tablet
Moexipril hcl 15 mg tablet 1.48 USD tablet
Moexipril hcl 7.5 mg tablet 1.41 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility Soluble (about 10% weight-to-volume) in distilled water at room temperature as HCl salt. Not Available
logP 2.7 Not Available
Predicted Properties
Property Value Source
water solubility 5.85e-03 g/l ALOGPS
logP 1.52 ALOGPS
logP 1.5 ChemAxon
logS -4.9 ALOGPS
pKa (strongest acidic) 3.46 ChemAxon
pKa (strongest basic) 5.2 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 114.4 ChemAxon
rotatable bond count 12 ChemAxon
refractivity 132.88 ChemAxon
polarizability 53.55 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Asmar R, Sayegh F, Tracz W, Hlawaty M, Olszowska M, Jourde M, Vincent M, Goujoun B, Maldonado J: Reversal of left ventricular hypertrophy with the ACE inhibitor moexipril in patients with essential hypertension. Acta Cardiol. 2002 Feb;57(1):31-2. Pubmed
  2. Blacher J, Raison J, Amah G, Schiemann AL, Stimpel M, Safar ME: Increased arterial distensibility in postmenopausal hypertensive women with and without hormone replacement therapy after acute administration of the ACE inhibitor moexipril. Cardiovasc Drugs Ther. 1998 Sep;12(4):409-14. Pubmed
  3. Brogden RN, Wiseman LR: Moexipril. A review of its use in the management of essential hypertension. Drugs. 1998 Jun;55(6):845-60. Pubmed
  4. Cawello W, Boekens H, Waitzinger J, Miller U: Moexipril shows a long duration of action related to an extended pharmacokinetic half-life and prolonged ACE inhibition. Int J Clin Pharmacol Ther. 2002 Jan;40(1):9-17. Pubmed
  5. Chrysant SG, Chrysant GS: Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol. 2004 Aug;44(8):827-36. Pubmed
  6. Chrysant SG, Chrysant GS: Pharmacological profile and clinical use of moexipril. Expert Rev Cardiovasc Ther. 2003 Sep;1(3):345-52. Pubmed
  7. Chrysant GS, Nguyen PK: Moexipril and left ventricular hypertrophy. Vasc Health Risk Manag. 2007;3(1):23-30. Pubmed
  8. Grass GM, Morehead WT: Evidence for site-specific absorption of a novel ACE inhibitor. Pharm Res. 1989 Sep;6(9):759-65. Pubmed
  9. Kalasz H, Petroianu G, Tekes K, Klebovich I, Ludanyi K, Gulyas Z: Metabolism of moexipril to moexiprilat: determination of in vitro metabolism using HPLC-ES-MS. Med Chem. 2007 Jan;3(1):101-6. Pubmed
  10. Persson B, Stimpel M: Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients. Eur J Clin Pharmacol. 1996;50(4):259-64. Pubmed
  11. Spinar J, Vitovec J: MORE—MOexipril and REgression of left ventricle hypertrophy in combination therapy A multicentric open label clinical trial. Int J Cardiol. 2005 Apr 20;100(2):199-206. Pubmed
  12. Stimpel M, Koch B, Oparil S: Antihypertensive treatment in postmenopausal women: results from a prospective, randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril) with a diuretic (hydrochlorothiazide). Cardiology. 1998 May;89(4):271-6. Pubmed
  13. White CM: Pharmacologic, pharmacokinetic, and therapeutic differences among ACE inhibitors. Pharmacotherapy. 1998 May-Jun;18(3):588-99. Pubmed
  14. White WB, Whelton A, Fox AA, Stimpel M, Kaihlanen PM: Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. J Clin Pharmacol. 1995 Mar;35(3):233-8. Pubmed
External Links
Resource Link
KEGG Compound C07704 Link_out
PubChem Compound 91270 Link_out
PubChem Substance 46508441 Link_out
ChemSpider 82418 Link_out
BindingDB 50084673 Link_out
Therapeutic Targets Database DAP000586 Link_out
PharmGKB PA164769059 Link_out
RxList http://www.rxlist.com/cgi/generic2/moexip.htm Link_out
Drugs.com http://www.drugs.com/cdi/moexipril.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/uni1468.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Moexipril Link_out
ATC Codes
  • C09AA13
AHFS Codes
  • 24:32.04
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amiloride Increased risk of hyperkalemia
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkalemia
Quinupristin This combination presents an increased risk of toxicity
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene Increased risk of hyperkalemia
Food Interactions
  • Herbs that may attenuate the antihypertensive effect of moexipril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of moexipril.
  • Moexipril may decrease the excretion of potassium. Salt substitutes containing potassium may increase the risk of hyperkalemia.
  • Take moexipril one hour before or two hours after meals.
Targets

1. Angiotensin-converting enzyme

Pharmacological action: yes
Actions: inhibitor

Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator

Organism class: human
UniProt ID: P12821 Link_out
Gene: ACE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Chrysant SG, Chrysant GS: Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol. 2004 Aug;44(8):827-36. Pubmed
  3. Edling O, Bao G, Feelisch M, Unger T, Gohlke P: Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. J Pharmacol Exp Ther. 1995 Nov;275(2):854-63. Pubmed
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. Pubmed

2. Angiotensin-converting enzyme 2

Pharmacological action: yes
Actions: inhibitor

Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin- 13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses

Organism class: human
UniProt ID: Q9BYF1 Link_out
Gene: ACE2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Chrysant SG, Chrysant GS: Pharmacological and clinical profile of moexipril: a concise review. J Clin Pharmacol. 2004 Aug;44(8):827-36. Pubmed
  3. Edling O, Bao G, Feelisch M, Unger T, Gohlke P: Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril. J Pharmacol Exp Ther. 1995 Nov;275(2):854-63. Pubmed
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: substrate

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. Epub 2008 Aug 19. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: substrate

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. Epub 2008 Aug 19. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19