What it is
Substance P is a neuropeptide of 11 amino acids: RPKPQQFFGLM, with the final methionine capped as an amide. UniProt's record (P20366) shows it cut from protachykinin-1, a 129-residue precursor that also yields neurokinin A and neuropeptide K. The family name for these peptides is tachykinins; UniProt describes them as peptides that excite neurons, widen blood vessels and contract smooth muscle.
It is made by sensory nerve cells, especially the thin fibres that carry pain, and is also found throughout the brain and the gut wall.
How it was found
The molecule was known by its effect for forty years before anyone knew its structure. In 1931, Ulf von Euler and John Gaddum reported an unidentified substance in extracts of horse brain and intestine that lowered blood pressure and contracted gut muscle (Journal of Physiology, PMID 16994201).
The structure came in two steps. Chang and Leeman isolated it from bovine hypothalamus in 1970 (J Biol Chem, PMID 5456150), and in 1971 Chang, Leeman and colleagues published its amino-acid sequence (Nature New Biology, PMID 5285346).
What it does
UniProt's function annotation, summarising the literature, describes substance P as a ligand for the NK1 receptor (TACR1) and, more weakly, NK3. Through these it:
| Action | What it means |
|---|---|
| Excites nerve cells | Carries and amplifies pain signals |
| Widens blood vessels | Redness and swelling at the site |
| Activates mast cells (via MRGPRX2) | Release of histamine and other inflammatory signals |
| Contracts smooth muscle | Gut and airway tightening |
Together these are called neurogenic inflammation: inflammation started by nerves rather than by an infection. Much of this map comes from animal and cell work; the human evidence is strongest for what happens when the receptor is blocked.
Blocking it: the approved drugs
No medicine gives substance P to anyone. The drugs that reached the market block its NK1 receptor. The first, aprepitant (Emend), was approved on 26 March 2003 (NDA021549); its label calls it "a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors" and records its use with ondansetron and dexamethasone against nausea and vomiting from chemotherapy. These blockers are small molecules, not peptides, and the label approves them for nausea and vomiting only.
Where it stands
openFDA's Drugs@FDA returns no application with substance P as the active ingredient (2026-10-03). PubMed returns 26,726 records, 323 tagged as randomised controlled trials — nearly all testing the blockers or measuring the peptide, not giving it.
Related reading
Substance P's job overlaps with bradykinin, another short peptide that widens blood vessels and sensitises pain nerves, and with VIP, a gut and nerve peptide. For how peptides are discussed as anti-inflammatory products, see peptides for inflammation.