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Identification
NameMoexipril
Accession NumberDB00691  (APRD01120)
Typesmall molecule
Groupsapproved
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
Synonyms
SynonymLanguageCode
MoexiprilNot AvailableNot Available
MoexiprilumLatinINN
UnireticNot AvailableNot Available
UnivascNot AvailableNot Available
Salts
Name/CAS Structure Properties
Moexipril Hydrochloride
Thumb
  • InChI Key: JXRAXHBVZQZSIC-JKVLGAQCSA-N
  • Monoisotopic Mass: 534.213279191
  • Average Mass: 535.029
DBSALT000504
Brand names
NameCompany
UnivascSchwarz
Brand mixtures
Brand NameIngredients
Unireticmoexipril + hydrochlorothiazide
Categories
CAS number103775-10-6
WeightAverage: 498.5681
Monoisotopic: 498.236601452
Chemical FormulaC27H34N2O7
InChI KeyUWWDHYUMIORJTA-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentPeptides
Alternative parentsAlpha Amino Acid Esters; Alpha Amino Acid Amides; Phenylpropylamines; Isoquinolines and Derivatives; Anisoles; Fatty Acid Esters; Alkyl Aryl Ethers; Dicarboxylic Acids and Derivatives; Tertiary Carboxylic Acid Amides; Tertiary Amines; Carboxylic Acid Esters; Enolates; Polyamines; Carboxylic Acids; Dialkylamines
Substituentsalpha-amino acid ester; alpha-amino acid amide; alpha-amino acid or derivative; phenylpropylamine; isoquinoline; anisole; phenol ether; fatty acid ester; alkyl aryl ether; benzene; dicarboxylic acid derivative; tertiary carboxylic acid amide; tertiary amine; carboxamide group; carboxylic acid ester; polyamine; ether; secondary amine; carboxylic acid; enolate; secondary aliphatic amine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
Pharmacology
IndicationFor the treatment of hypertension.
PharmacodynamicsMoexipril 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 actionMoexipril 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.
AbsorptionMoexipril 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 bindingMoexiprilat 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.

SubstrateEnzymesProduct
Moexipril
Not Available
MoexiprilatDetails
Route of eliminationMoexiprilat undergoes renal elimination.
Half lifeMoexipril elimination half-life is approximately 1 hour. Moexiprilat elimination half-life is 2 to 9 hours.
Clearance
  • 441 mL/min
ToxicityHuman 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
PathwayCategorySMPDB ID
Moexipril Action PathwayDrug actionSMP00151
Moexipril Metabolism PathwayDrug metabolismSMP00595
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.5775
Blood Brain Barrier - 0.9022
Caco-2 permeable - 0.7313
P-glycoprotein substrate Substrate 0.9085
P-glycoprotein inhibitor I Inhibitor 0.5919
P-glycoprotein inhibitor II Inhibitor 0.8157
Renal organic cation transporter Non-inhibitor 0.8146
CYP450 2C9 substrate Non-substrate 0.8588
CYP450 2D6 substrate Non-substrate 0.8369
CYP450 3A4 substrate Substrate 0.7014
CYP450 1A2 substrate Non-inhibitor 0.8205
CYP450 2C9 substrate Non-inhibitor 0.5961
CYP450 2D6 substrate Non-inhibitor 0.8261
CYP450 2C19 substrate Non-inhibitor 0.6592
CYP450 3A4 substrate Non-inhibitor 0.5935
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6861
Ames test Non AMES toxic 0.8358
Carcinogenicity Non-carcinogens 0.9378
Biodegradation Not ready biodegradable 0.9762
Rat acute toxicity 2.5131 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9715
hERG inhibition (predictor II) Inhibitor 0.8751
Pharmacoeconomics
Manufacturers
  • Apotex inc
  • Glenmark generics ltd
  • Paddock laboratories inc
  • Teva pharmaceuticals usa inc
  • Schwarz pharma inc
Packagers
Dosage forms
FormRouteStrength
TabletOral15 mg
Tablet, film coatedOral7.5 mg
Prices
Unit descriptionCostUnit
Univasc 15 mg tablet2.44USDtablet
Univasc 7.5 mg tablet2.13USDtablet
Moexipril hcl 15 mg tablet1.48USDtablet
Moexipril hcl 7.5 mg tablet1.41USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubilitySoluble (about 10% weight-to-volume) in distilled water at room temperature as HCl salt.Not Available
logP2.7Not Available
Predicted Properties
PropertyValueSource
water solubility5.85e-03 g/lALOGPS
logP1.52ALOGPS
logP1.5ChemAxon
logS-4.9ALOGPS
pKa (strongest acidic)3.46ChemAxon
pKa (strongest basic)5.2ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count7ChemAxon
hydrogen donor count2ChemAxon
polar surface area114.4ChemAxon
rotatable bond count12ChemAxon
refractivity132.88ChemAxon
polarizability53.55ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot 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
ResourceLink
KEGG CompoundC07704
PubChem Compound91270
PubChem Substance46508441
ChemSpider82418
BindingDB50084673
Therapeutic Targets DatabaseDAP000586
PharmGKBPA164769059
RxListhttp://www.rxlist.com/cgi/generic2/moexip.htm
Drugs.comhttp://www.drugs.com/cdi/moexipril.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/uni1468.shtml
WikipediaMoexipril
ATC CodesC09AA13
AHFS Codes
  • 24:32.04
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmilorideIncreased risk of hyperkalemia
Azilsartan medoxomilPharmacodynamic synergism: dual blockade of renin-angiotensin system. Increases risks of hypotension, hyperkalemia, renal impairment.
IcatibantIcatibant may attenuate the antihypertensive effect of ACE inhibitors by pharmacodynamic antagonism. Monitor concomitant therapy closely.
LithiumThe ACE inhibitor increases serum levels of lithium
PotassiumIncreased risk of hyperkalemia
QuinupristinThis combination presents an increased risk of toxicity
TizanidineTizanidine increases the risk of hypotension with the ACE inhibitor
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
TriamtereneIncreased 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Angiotensin-converting enzyme P12821 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Angiotensin-converting enzyme 2 Q9BYF1 Details

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. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

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. Solute carrier family 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11