Substance P (1-7): nerve-signaling fragment that lowers blood pressure and eases opioid withdrawal
A naturally occurring fragment of substance P, a pain and inflammation messenger; lowers blood pressure and slows heart rate in the brain's cardiovascular control center, and may reduce opioid withdrawal signs in mice, used only as a lab research tool.
- Class
- Endogenous neuropeptide / tachykinin
- Status
- No approved therapeutic status identified in attached sources
- Main caveat
- Card written from catalog and overview text only (SB + CU sources); no study, trial, or assay data are individually attached.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
Named peptide fragment — synthesized for research; ClinicalTrials.gov trials registered for parent compound or class
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Endogenous peptide fragment — receptor binding/activity established in published literature; CT.gov evidence
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What this is
Substance P (1-7) is a naturally occurring fragment of substance P, a well-known signaling peptide found throughout the nervous and immune systems. It consists of the first seven amino acids of the full 11-residue substance P sequence — the same N-terminal stretch that anchors substance P to its primary receptor. Researchers use this fragment to probe how the NK1 receptor (also called the neurokinin-1 receptor) recognizes its ligand, and to tease apart which part of substance P is responsible for which biological effects.
What it does
In the cardiovascular and autonomic nervous system, Substance P (1-7) has been reported to lower blood pressure and slow heart rate when acting in the nucleus tractus solitarius, a brainstem region that integrates cardiovascular control signals. Separately, studies in mice have found that this fragment can reduce signs of opioid withdrawal, suggesting it modulates pain and stress circuitry independently of its role in the immune system.
At the receptor level, substance P and the NK1 receptor are a well-characterized signaling pair. When substance P (or fragments that retain receptor binding) engages NK1R — a G protein-coupled receptor — this triggers activation of NF-κB and the release of proinflammatory cytokines, as reviewed by Douglas and colleagues (Annals of the New York Academy of Sciences, 2011). NK1R itself exists in two forms: a full-length isoform and a truncated isoform, which differ in their functional significance (Douglas et al. 2011).
Evidence
- Human: No human clinical trials for Substance P (1-7) specifically are known from published literature.
- Animal: Depressor and bradycardic effects have been reported in animal models following administration into the nucleus tractus solitarius; opioid withdrawal signs reduced in mice.
- In vitro: NK1R binding and downstream NF-κB/cytokine signaling characterized in cellular models (Douglas et al. 2011).
Mechanism
Substance P (1-7) retains the N-terminal sequence RPKPQQF from the full-length peptide RPKPQQFFGLM-NH2. The NK1 receptor (tacr1) is the primary target; binding to NK1R couples through G proteins to activate NF-κB and downstream proinflammatory cytokines (Douglas et al. 2011). Schank and colleagues (International Review of Neurobiology, 2017) have framed the SP/NK1R system as a stress-response pathway with functional parallels to corticotropin-releasing factor (CRF) signaling — a framework that helps contextualize Substance P (1-7)'s reported effects on autonomic cardiovascular tone and opioid-related behavior.
NK1R is ubiquitous across species and tissues. Its two isoforms — full-length and truncated — have distinct functional profiles (Douglas et al. 2011), a distinction relevant to interpreting receptor binding studies with short fragments such as SP(1-7).
Related peptides
- Substance P (full-length, RPKPQQFFGLM-NH2) is the parent peptide from which this fragment derives; the C-terminal residues FGLM are absent in SP(1-7), differentiating their receptor pharmacology.
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Could this fragment calm withdrawal symptoms by acting on a different target in the brain stem?
If confirmed, it could point to an entirely new drug strategy for opioid withdrawal that avoids the inflammatory risks of activating the standard substance P receptor. This matters for the millions of people seeking safer withdrawal treatments.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9104166626930237 | boltz-2 |
| ranking score | 0.7384291887283325 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 1.480 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10633,
sequence = {RPKPQQF},
target = {tacr1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}