Neurokinin Antagonists intermediate
Ulefipant
NK1 receptor antagonist peptide under investigation for chemotherapy-induced nausea and vomiting.
By Encyclopeptide Editorial | 2 min read
NK1-antagonist antiemetic CINV substance-P
Chemical Identity
| Property | Value |
|---|---|
| Molecular Weight | ~1200 Da |
| Peptide Class | NK1 Receptor Antagonist |
| Route | IV, oral |
Structure
Ulefipant is a peptidomimetic NK1 receptor antagonist that blocks substance P signaling. While not a classical peptide, it represents the development of peptide-mimetic therapeutics targeting neuropeptide receptors involved in emesis and pain pathways.
Mechanism of Action
Ulefipant competitively blocks the neurokinin 1 (NK1) receptor, the primary receptor for substance P in the brainstem vomiting center. By blocking substance P binding in the area postrema and nucleus tractus solitarius, it prevents both acute and delayed phases of chemotherapy-induced nausea and vomiting.
Clinical Applications
- Chemotherapy-induced nausea and vomiting: Highly emetogenic regimens
- Delayed CINV: Particularly effective for delayed phase
- Combination therapy: With 5-HT3 antagonists and dexamethasone
- Investigational: Newer NK1 antagonists in development
Pharmacology
- Brain penetration: High (crosses BBB)
- Duration: 24-48 hours
- Combination: Enhanced with 5-HT3 antagonists
- Selectivity: High affinity for NK1 receptor
References
- Gralla, R.J., et al. (2014). NK1 receptor antagonists for CINV. Lancet Oncology, 15, 894-898.
- Navari, R.M. (2013). Management of chemotherapy-induced nausea. New England Journal of Medicine, 368, 1614-1621.
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