Miscellaneous & Research; Cognitive & Neuroprotection

Substance P

Substance P is the eleven-amino-acid messenger nerves release at the point where pain is signalled, and it is a large part of why a sting turns red and swells — it widens vessels, leaks plasma into tissue and degranulates mast cells. In research it is used as a provocation rather than a treatment: infused into 21 healthy volunteers in a double-blind crossover, it produced headache within twelve hours in 15 of them against 2 on placebo, with measurable dilation of the superficial temporal artery. That reliability is what makes it useful, because a blocking drug can be measured against it. There is no approved use of substance P itself.

Last updated 12 August 2026

Studied forNociception research · Neurogenic inflammation studies · Migraine provocation research

Evidence on file1 randomised human trial · 1 animal study · 1 citation not yet graded

Strongest sourceNeurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation (Clinical Pharmacology & T… (randomised human trial)

Mechanism

Agonist at the neurokinin-1 receptor, driving vasodilation, plasma extravasation, mast cell degranulation and excitatory pain transmission.

Reported effects

What sources associate with this compound. Reported categories, not outcomes we have graded — each would need its own citation and rung.

Nociception research
Neurogenic inflammation studies
Migraine provocation research

Dosing on file unverified

1.5-4.0 pmol/kg/min IV infusion over 20-60 min; 0.5, 1, 1.5 pmol/kg/min over 60 min; 1.5-4.0 pmol/kg/min IV infusion over 20 min (research/provocative testing)

Carried from a source that labels it unverified, and reproduced with that label attached. A record of what is reported, not a recommendation. No citation on this page establishes it.

Literature on file 3

animal in vivo
Cyclosporin A is a substance P (tachykinin NK1) receptor antagonist (European Journal of Pharmacology: Molecular Pharmacology 1995, cited 22x) graded on: an animal model — read from the indexed abstract — “pigs”
human RCT
Neurokinin-1 receptor antagonist R116301 inhibits substance P-induced venodilation (Clinical Pharmacology & Therapeutics 1999, cited 8x) graded on: names a randomised controlled trial — the indexed publication type — “Randomized Controlled”

Not graded

1 citation whose study design could not be read from the title. Left ungraded rather than guessed at.

not graded
NCT06959004: Substance P-Induced Migraine Attacks Without Aura: A Randomized Clinical Trial graded on: NCT06959004 is recruiting and has posted no results - a registration, not a reported outcome — “NCT06959004”

Identity

Space-filling 3D model of Substance P, carbon grey, nitrogen blue, oxygen red — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

2D chemical structure of Substance P — Built from the SMILES on this record — the atoms and bonds are exact. The shape is **one computed low-energy pose**, not a measured structure: a flexible peptide in solution has no single conformation, and where the SMILES leaves a stereocentre undefined the pose commits to one arbitrarily. The skeletal formula below claims connectivity and nothing more, which is what we actually know.

Molecular weight: 1347.6
Molecular formula: C63H98N18O13S
CAS number: 33507-63-0
PubChem CID: 36511
UniProt: P20366
InChI key: ADNPLDHMAVUMIW-CUZNLEPHSA-N
SMILES: CC(C)C[C@@H](C(=O)N[C@@H](CCSC)C(=O)N)NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCCN)NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCN=C(N)N)N
InChI: InChI=1S/C63H98N18O13S/c1-37(2)33-45(57(89)74-41(53(68)85)27-32-95-3)73-52(84)36-72-54(86)46(34-38-15-6-4-7-16-38)78-58(90)47(35-39-17-8-5-9-18-39)79-56(88)42(23-25-50(66)82)75-55(87)43(24-26-51(67)83)76-59(91)49-22-14-31-81(49)62(94)44(20-10-11-28-64)77-60(92)48-21-13-30-80(48)61(93)40(65)19-12-29-71-63(69)70/h4-9,15-18,37,40-49H,10-14,19-36,64-65H2,1-3H3,(H2,66,82)(H2,67,83)(H2,68,85)(H,72,86)(H,73,84)(H,74,89)(H,75,87)(H,76,91)(H,77,92)(H,78,90)(H,79,88)(H4,69,70,71)/t40-,41-,42-,43-,44-,45-,46-,47-,48-,49-/m0/s1

Also called

Substance P (Research)

Caveat on these identifiers

Source files disagreed on evidence tier for this peptide.

Notes unverified prose

2025 human migraine studies; NCT06959004; 2025 human studies: 1.5 pmol/kg/min and 4.0 pmol/kg/min IV for headache induction; research use only

Not on file 2

1 of the 8 fields we track hold nothing on this record, and each says why. 1 further absence is named below. A blank field is a bug; a named absence is a finding.

amino-acid sequencenothing we hold supplies it
half-lifenothing we hold supplies it

Each field links to every other record missing the same thing. The full ledger holds 765 gaps across 163 records.