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Wikipedia - Enalapril

Not to be confused with Allopurinol.
Enalapril
Systematic (IUPAC) name
(2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid

(Diagrams above are enalapril and enalaprilat, respectively. Data below refers to enalapril unless indicated)
Identifiers
CAS number 75847-73-3
ATC code C09AA02
PubChem CID 5388962
DrugBank APRD00510
ChemSpider 4534998
Chemical data
Formula C20H28N2O5 
Mol. mass 376.447 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 60% (oral)
Metabolism hepatic (to enalaprilat)
Half-life 11 hours (enalaprilat)
Excretion renal
Therapeutic considerations
Pregnancy cat. C,D
Legal status ? Prescription only
Routes I.V. and P.O.
 YesY(what is this?)  (verify)

Enalapril (marketed as Renitec and Vasotec) is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension and some types of chronic heart failure. ACE raises blood pressure by constricting blood vessels. ACE inhibitors like enalapril prevent this effect. Enalapril has been shown to lower the death rate in systolic heart failure.[1] Enalapril was the first member of the group of ACE inhibitors known as the dicarboxylate-containing ACE inhibitors.

Contents

[edit] Development

Enalapril is a treatment for high blood pressure that works by modulating the renin-angiotensin-aldosterone (RAS) system.

Squibb developed the first inhibitor, captopril, but it had adverse effects such as a metallic taste (which, as it turned out, was due to the sulfhydryl group). Merck & Co. developed enalapril as a competing product.

[edit] Enalaprilat

Enalaprilat, the first dicarboxylate-containing ACE inhibitor, was developed partly to overcome these limitations of captopril. The sulfhydryl-moiety was replaced by a carboxylate-moiety, but additional modifications were required in its structure-based design to achieve a similar potency to captopril.

Enalaprilat, however, had a problem of its own. The consequence of the structural modifications was that it proved to have unfavourable ionisation characteristics to allow sufficient potency for oral administration (in tablets). Thus enalaprilat was only suitable for intravenous administration. This was overcome by the researchers at Merck by the esterification of enalaprilat with ethanol to produce enalapril.

As a prodrug, enalapril is metabolised in vivo to the active form enalaprilat by various esterases. Peak plasma enalaprilat concentrations occur 2 to 4 hours after oral enalapril administration. Elimination thereafter is biphasic, with an initial phase which reflects renal filtration (elimination half-life 2 to 6 hours) and a subsequent prolonged phase (elimination half-life 36 hours), the latter representing equilibration of drug from tissue distribution sites.

The prolonged phase does not contribute to drug accumulation on repeated administration but is thought to be of pharmacological significance in mediating drug effects. Renal impairment [particularly creatinine clearance < 20 ml/min (< 1.2 L/h)] results in significant accumulation of enalaprilat and necessitates dosage reduction. Accumulation is probably the cause of reduced elimination in healthy elderly individuals and in patients with concomitant diabetes, hypertension and heart failure.

[edit] A prototype for others

Most importantly, perhaps, the QSAR-based modifications in structure serendipitously led to an improved understanding of the structure of ACE which aided in the development of subsequent carboxylate-containing ACE inhibitors.

Enalapril is a prodrug that is converted by deesterification to converting enzyme inhibitor, enalaprilat, with effects similar to those of captopril. Enalaprilat itself is available only for intravenous use, primarily for hypertensive emergencies.

[edit] Side Effects

Most common side effects include hypotension, dizziness when standing up, and dry cough.[2]

[edit] Chem

Enalapril reductive amination.png

Patchett, A. A.; in Chronicles of Drug Discovery, Vol. 3; Lednicer, D., ed., ACS Books, Washington, DC, 1993, 125.

[edit] References

  1. ^ McMurray JJV, Systolic heart failure, N Engl J Med, 362:228, Jan. 21, 2010)
  2. ^ Listed at http://www.drugs.com.

[edit] External links

v • d • e
Antihypertensives: agents acting on the renin-angiotensin system (C09)
ACE inhibitors
("-pril")
AIIRAs/
("-sartan")
Renin inhibitors/
("-kiren")
Retrieved from "http://en.wikipedia.org/wiki/Enalapril"

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Enalapril".

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