Rotigaptide

Summary

Rotigaptide is an investigational hexapeptide analogue designed to prevent cardiac arrhythmias by enhancing gap junction coupling through connexin 43 stabilization. It has been evaluated in preclinical and early clinical studies for atrial and ventricular arrhythmias. Development was primarily pursued by Zealand Pharma.

Mechanism of Action

Rotigaptide (ZP123) is a synthetic peptide analogue of antiarrhythmic peptide AAP10. It acts by enhancing gap junction intercellular communication, specifically by preventing the dephosphorylation of connexin 43 (Cx43) and maintaining gap junction conductance between cardiomyocytes, thereby reducing the risk of reentrant arrhythmias.

Routes of Administration

Goals & Uses

• Prevention of atrial fibrillationCardiovascular / AntiarrhythmicModerate
• Cardioprotection during ischemiaCardiovascular / CardioprotectionLow
• Prevention of ventricular arrhythmiasCardiovascular / AntiarrhythmicModerate

Contraindications

• Hypersensitivity to rotigaptide or peptide excipientsAllergicHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• HypotensionCardiovascularUncommonLow blood pressure

Drug Interactions

• Antiarrhythmic agentsModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Severe hepatic or renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative

Regulatory Status

• European UnionInvestigationalNo EMA approval; early-phase clinical trials conducted in Europe.
• United StatesInvestigationalNo FDA approval; investigated under IND. Clinical development has not progressed to NDA.
• United KingdomInvestigationalNot approved by MHRA; research/investigational status only.

Rotigaptide has not received regulatory approval in any jurisdiction. Clinical development appears to have stalled after Phase I/II studies. It remains a research/investigational compound.

Evidence & Sources

No sources recorded yet.