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a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/09/04 00:56:48」(JST)

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Moexipril hydrochloride is a potent orally active nonsulfhydryl angiotensin converting enzyme inhibitor (ACE inhibitor)^[1] which is used for the treatment of hypertension and congestive heart failure. Moexipril can be administered alone or with other antihypertensives or diuretics.^[2] It works by inhibiting the conversion of angiotensin I to angiotensin II.^[3] Moexipril is available from Schwarz'Pharma under the trade name Univasc.^[3]^[4]

Pharmacology

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.^[5] Moexipril is incompletely absorbed after oral administration, and its bioavailability is low.^[6] The long pharmacokinetic half-life and persistent ACE inhibition of moexipril allows once-daily administration.^[7]

Moexipril is highly lipophilic,^[2] and is in the same hydrophobic range as quinapril, benazepril, and ramipril.^[7] 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.^[8]

It has additional PDE4-inhibiting effects.^[9]

Side effects

Moexipril is generally well tolerated in elderly patients with hypertension.^[10] Hypotension, dizziness, increased cough, diarrhea, flu syndrome, fatigue, and flushing have been found to affect less than 6% of patients who were prescribed moexipril.^[3]^[10]

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.^[11] The cardioprotective effects of ACE inhibitors are mediated through a combination of angiotensin II inhibition and bradykinin proliferation.^[8]^[12] Increased levels of bradykinin stimulate in the production of prostaglandin E2^[13] and nitric oxide,^[12] which cause vasodilation and continue to exert antiproliferative effects.^[8] 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)^[14] and the transforming growth factor beta-1 (TGF-β1),^[15] 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.^[12] Other ACE inhibitors have also been found to produce these actions, as well.

References

^ Hochadel, Maryanne, ed. (2006). The AARP Guide to Pills. Sterling Publishing Company. p. 640. ISBN 978-1-4027-1740-6. Retrieved 2009-10-09.
^ ^a ^b Belal, F.F, K.M. Metwaly, and S.M. Amer. "Development of Membrane Electrodes for the Specific Determination of Moexipril Hydrochloride in Dosage Forms and Biological Fluids." Portugaliae Electrochimica Acta. 27.4 (2009): 463-475.
^ ^a ^b ^c Rodgers, Katie, Michael C Vinson, and Marvin W Davis. "Breakthroughs: New drug approvals of 1995 -- part 1." Advanstar Communications, Inc. 140.3 (1996): 84.
^ Dart, Richard C. (2004). Medical toxicology. Lippincott Williams & Wilkins. p. 647. ISBN 978-0-7817-2845-4. Retrieved 2009-10-09.
^ Kalasz, H, G. Petroianu, K. Tekes, I. Klebovich, K. Ludanyi, et al. “Metabolism of moexipril to moexiprilat: determination of in vitro metabolism using HPLC-ES-MS.” Medicinal Chemistry. 3 (2007): 101-106.
^ Chrysant, George S, PK Nguyen. “Moexipril and left ventricular hypertrophy.” Vascular Health Risk Management. 3.1 (2007): 23-30.
^ ^a ^b Cawello W, H. Boekens, J. Waitzinger, et al. “Moexipril shows a long duration of action related to an extended pharmacokinetic half-life and prolonged ACE-inhibition.” Int J Clin Pharmacol Ther. 40 (2002): 9-17.
^ ^a ^b ^c Chrysant, SG. “Vascular remodeling: the role of angiotensin-converting enzyme inhibitors.” American Heart Journal. 135.2 (1998): 21-30.
^ Cameron, RT; Coleman, RG; Day, JP; Yalla, KC; Houslay, MD; Adams, DR; Shoichet, BK; Baillie, GS (May 2013). "Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)". Biochemical Pharmacology 85 (9): 1297–1305. doi:10.1016/j.bcp.2013.02.026. PMC 3625111. PMID 23473803.
^ ^a ^b White, WB, and M Stimpel. "Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension." Journal of human hypertension. 9.11 (1995): 879-884.
^ Rosendorff, C. “The Renin-Angiotensin System and Vascular Hypertrophy.” Journal of the American College of Cardiology. 28 (1996): 803-812.
^ ^a ^b ^c Hartman, J.C. “The role of bradykinin and nitric oxide in the cardioprotective action of ACE inhibitors.” The Annals of Thoracic Surgery. 60.3 (1995): 789-792.
^ Jaiswal, N, DI Diz, MC Chappell, MC Khosia, CM Ferrario. “Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors.” Hypertension. 19.2 (1992): 49-55.
^ Phillips, PA. “Interaction between endothelin and angiotensin II.” Clinical and Experimental Pharmacology and Physiology. 26.7. (1999): 517-518.
^ Youn, TJ, HS Kim, BH Oh. “Ventricular remodeling and transforming growth factor-beta 1 mRNA expression after nontransmural myocardial infarction in rats: effects of angiotensin converting enzyme inhibition and angiotensin II type 1 receptor blockade.” Basic research in cardiology. 94.4 (1999): 246-253.

UpToDate Contents

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1. 患者情報：成人における高血圧治療（詳細） high blood pressure treatment in adults beyond the basics

English Journal

Comparative study between univariate spectrophotometry and multivariate calibration as analytical tools for simultaneous quantitation of Moexipril and Hydrochlorothiazide.

Tawakkol SM1, Farouk M2, Elaziz OA2, Hemdan A3, Shehata MA4.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Dec 10;133:300-6. doi: 10.1016/j.saa.2014.05.061. Epub 2014 Jun 5.
Three simple, accurate, reproducible, and selective methods have been developed and subsequently validated for the simultaneous determination of Moexipril (MOX) and Hydrochlorothiazide (HCTZ) in pharmaceutical dosage form. The first method is the new extended ratio subtraction method (EXRSM) coupled
PMID 24954754

Crystal structure of [(2S)-1-[(3S)-3-carboxy-6,7-dimethoxy-1,2,3,4-tetra-hydroisoquinolin-2-yl]-1-oxopropan-2-yl][(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]azanium chloride acetonitrile monosolvate.

Li AZ1, Xu WJ1.
Acta crystallographica. Section E, Structure reports online.Acta Crystallogr Sect E Struct Rep Online.2014 Sep 24;70(Pt 10):o1126-7. doi: 10.1107/S160053681402090X. eCollection 2014.
The title compound (trivial name moexipril hydro-chloride) crystallizes as the aceto-nitrile monosolvate, C27H35N2O7 (+)·Cl(-)·C2H3N, with the salt comprising a U-shaped cation and a chloride anion. The conformation of the cation is stabilized by a weak intra-molecular N(+)-H⋯O hydrogen bond and
PMID 25484709

Electrochemistry of moexipril: experimental and computational approach and voltammetric determination.

Taşdemir HI, Kiliç E.
Die Pharmazie.Pharmazie.2014 Sep;69(9):648-54.
The electrochemistry of moexipril (MOE) was studied by electrochemical methods with theoretical calculations performed at B3LYP/6-31 + G (d)//AM1. Cyclic voltammetric studies were carried out based on a reversible and adsorption-controlled reduction peak at -1.35 V on a hanging mercury drop electrod
PMID 25272934

「モエキシプリル」

Moexipril
Systematic (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
Clinical data
Trade names	Univasc
AHFS/Drugs.com	monograph
MedlinePlus	a695018
Pregnancy; category	US: D (Evidence of risk);
Legal status	UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	13-22%
Protein binding	90%
Metabolism	Hepatic (active metabolite, moexiprilat)
Biological half-life	1 hour; 2-9 hours (active metabolite)
Excretion	50% (faeces), 13% (urine)
Identifiers
CAS Registry Number	103775-10-6
ATC code	C09AA13
PubChem	CID: 91270
IUPHAR/BPS	6571
DrugBank	DB00691
ChemSpider	82418
UNII	WT87C52TJZ
KEGG	D08225
ChEMBL	CHEMBL1165
Chemical data
Formula	C27H34N2O7
Molecular mass	498.568 g/mol
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