Overview
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In plain language
Substance P is a natural messenger molecule of 11 amino acids found in nerves. It helps carry pain signals and can trigger inflammation and swelling.
It was discovered in 1931, and its name comes from the "P" (for powder) used in the original lab notes. Drugs that block its receptor are used to prevent nausea and vomiting from chemotherapy. Substance P itself is not a drug.
For students
Substance P (RPKPQQFFGLM-NH2, about 1,348 Da) was discovered by Ulf von Euler and John Gaddum in 1931 as a gut-contracting extract. Susan Leeman's group sequenced it in 1971. It belongs to the tachykinin family, which shares the C-terminal motif Phe-X-Gly-Leu-Met-NH2.
It acts mainly on the NK1 receptor. Released from sensory nerve endings, it causes blood vessels to widen and leak (neurogenic inflammation) and passes pain signals in the spinal cord. In the brainstem, NK1 signaling contributes to vomiting.
For researchers and instructors
Therapeutics. NK1 antagonists such as aprepitant (approved 2003) prevent chemotherapy-induced and postoperative nausea and vomiting.
Failed translation. NK1 antagonists failed as analgesics and antidepressants despite strong animal data, a well-known case in drug-development history.
Status. Natural neuropeptide; not a drug.
Molecular identity
- Amino acids
- 11
- Molecular weight
- ~1,347.6 Da
- Formula
- C₆₃H₉₈N₁₈O₁₃S
- Sequence
- RPKPQQFFGLM-NH₂
Sequence map
Hydropathy
Kyte–Doolittle score per residue. Positive values are water-repelling.
Origin and history
Substance P was discovered in 1931 by Ulf von Euler and John Gaddum in London, in extracts of horse brain and gut that made intestines contract. The “P” simply stood for the dried “preparation” (powder) they used.
It took 40 years to identify: in 1971 Susan Leeman’s lab sequenced its 11 amino acids. It became known as a key pain and inflammation signal. Drugs that block its receptor, starting with aprepitant in 2003, now prevent nausea from chemotherapy.
Key people
- Ulf von EulerCo-discoverer; Nobel Prize 1970 for other work
- John GaddumCo-discoverer
- Susan LeemanSequenced it (1971)
Timeline
- 1931
Substance P discovered
- 1971
Sequenced
- 2003
First receptor-blocking drug, aprepitant, approved
See every peptide on one history timeline.
Human evidence
Not used as a treatment. Drugs that block its receptor, such as aprepitant, are approved to prevent chemotherapy-induced nausea.
Registration and enrollment are not proof of benefit; check study results directly.
Explore original publications and distinguish preclinical findings from controlled human evidence.
Safety and regulatory status
See every compound on the regulatory tracker.
Natural neuropeptide; not a drug.
This profile is educational and does not provide treatment, dosing or sourcing guidance.
Sources
- PubMed literature search: Substance P
- PubChem compound search: Substance P
- PubMed: Chang Leeman 1971 substance P
- ClinicalTrials.gov search: Substance P
Hernandez Gener, E. (2026, November 7). Substance P: molecular data, research history and evidence. VALREXA Biosciences. https://valrexa.com/peptides/substance-p.html
APA style · Last reviewed November 7, 2026 · Our editorial standardsLast reviewed November 7, 2026. Trial and regulatory status can change; confirm in the linked registries. This profile is educational and is not medical advice, a treatment recommendation, or dosing or sourcing guidance. Report an error · Corrections policy