Enalkiren

Summary

Enalkiren (A-64662) is an early peptidomimetic renin inhibitor developed in the late 1980s and early 1990s by Abbott Laboratories. It was investigated as an antihypertensive agent but was never approved for clinical use, primarily due to poor oral bioavailability requiring parenteral administration and the subsequent development of more drug-like small-molecule renin inhibitors (e.g., aliskiren).

Mechanism of Action

Competitive inhibitor of renin, the aspartyl protease that cleaves angiotensinogen to angiotensin I. By blocking renin, enalkiren reduces the generation of angiotensin I and subsequently angiotensin II, leading to vasodilation and decreased aldosterone secretion.

Routes of Administration

Goals & Uses

• Antihypertensive effectCardiovascularModerate
• Heart failure managementCardiovascularLow
• RAAS suppressionCardiovascular/EndocrineModerate

Contraindications

• Hypersensitivity to enalkiren or excipientsImmunologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Bilateral renal artery stenosisVascular/RenalHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HypotensionCardiovascularCommonLow blood pressure
• Renal function impairmentRenalUncommon
• HyperkalemiaElectrolyte ImbalanceUncommon

Drug Interactions

• Potassium-sparing diuretics / potassium supplementsModerate
• ACE inhibitors / ARBsHigh
• NSAIDsModerateMay increase renal risk in susceptible patients

Population Constraints

• Patients with renal impairmentOrgan ImpairmentRelative
• Pregnant womenReproductiveAbsolute
• Volume-depleted patientsCardiovascularRelative

Regulatory Status

• European UnionUnapprovedNo regulatory submission or approval; remained a research compound.
• United StatesUnapprovedInvestigated in Phase II clinical trials; never submitted for or received FDA approval.
• United KingdomUnapprovedNo approval; used only in clinical research settings.

Never received regulatory approval in any jurisdiction. Remained a research/investigational compound. Development was discontinued in favor of orally bioavailable renin inhibitors.

Evidence & Sources

No sources recorded yet.