Metkephamid

Summary

Metkephamid (LY127623) is a synthetic enkephalin analog developed in the late 1970s–1980s as an analgesic with preferential delta-opioid receptor activity. It demonstrated analgesic efficacy in early clinical trials but was not advanced to regulatory approval. It remains a pharmacological research tool for studying opioid receptor subtypes.

Mechanism of Action

Selective agonist at delta-opioid receptors with some mu-opioid receptor activity; mimics endogenous enkephalins to produce analgesia by inhibiting adenylyl cyclase and modulating ion channels, reducing nociceptive signaling.

Routes of Administration

Goals & Uses

• Reduced respiratory depression vs. mu-opioidsSafety Profile InvestigationLow
• Opioid receptor subtype researchPharmacological ResearchHigh
• AnalgesiaPain ManagementModerate

Contraindications

• Known hypersensitivity to enkephalin analogsAllergyHigh
• Concurrent CNS depressant useDrug InteractionModerate

Adverse Effects

• DysphoriaPsychiatricUncommon
• HypotensionCardiovascularUncommonLow blood pressure
• Nausea and vomitingGastrointestinalCommon
• Respiratory depressionRespiratoryUncommon
• SedationCNSCommon

Drug Interactions

• Other opioid analgesicsModerate
• BenzodiazepinesHigh
• NaloxoneLow

Population Constraints

• Pediatric patientsAgeRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Patients with respiratory insufficiencyPulmonaryRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionUnapprovedNo marketing authorization sought or granted in European jurisdictions.
• United StatesUnapprovedInvestigated in clinical trials by Eli Lilly in the 1980s; never submitted for or received FDA approval.
• United KingdomUnapprovedNo regulatory approval; remains a research compound only.

Never received regulatory approval in any major jurisdiction. Investigated in Phase I/II clinical trials primarily in the 1980s. Remains a research compound.

Evidence & Sources

No sources recorded yet.