Brain-pain research tool (M-15 / Galanin: Substance P chimera)
A lab-made hybrid peptide that blocks galanin's signals in the brain and spinal cord to study pain and nerve activity; used only as a lab research tool.
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.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
M-15 (also written as galanin-(1-13)-substance P-(5-11) amide) is a synthetic 20-amino-acid chimeric peptide built by fusing the front half of one neuropeptide, galanin, to the tail end of another, substance P. It was designed in the early 1990s as a research tool — the first reported high-affinity blocker of galanin's actions on neurons — and it remains a reference compound used to probe what galanin receptors do in the brain and spinal cord (Bartfai 1991; Langel 1992). The stored 20-letter sequence (GWTLNSAGYLLGPQQFFGLM) is the bare backbone; the active peptide carries a C-terminal amide inherited from the substance P portion, which is standard for this family and is not visible in the raw letter string.
History
The chimeric design strategy was introduced by Tamas Bartfai and colleagues at the Karolinska Institute, who reasoned that grafting the N-terminal recognition region of galanin onto the C-terminal "message" segment of substance P would produce a ligand that binds galanin receptors but does not transmit galanin's normal inhibitory signal (Bartfai 1991). The original 1991 report characterized M-15 as a 20-residue peptide that displaced radiolabeled galanin from binding sites in rat ventral hippocampus, midbrain, and spinal cord with an IC50 of approximately 0.1 nM (Bartfai 1991). A companion paper from the same group surveyed several related chimeras and identified galantide (galanin-(1-12)-Pro-substance P-(5-11) amide) as "the first galanin antagonist to be reported," establishing M-15 and galantide as the founding members of a small family of chimeric galanin-receptor ligands (Langel 1992). Their use as pharmacological tools was extended in the following years to dissect receptor subtypes — for example, Wynick and colleagues used M-15 to argue that the high-affinity galanin receptor on the rat anterior pituitary is distinct from the brain/gut receptor, because M-15's membrane binding there was markedly reduced (Wynick 1993).
What it does
In the brain regions where it has been tested, M-15 sits on galanin receptors without triggering galanin's usual response, and it blocks the natural peptide from doing so either. In the original characterization, M-15 reversed two well-known galanin effects: it blocked galanin's inhibition of evoked acetylcholine release in the hippocampus (measured in vivo) and it blocked galanin-induced hyperpolarization of locus coeruleus neurons in brain slices (Bartfai 1991). Because galanin tends to dampen the firing and transmitter release of the neurons it acts on, an antagonist like M-15 lifts that dampening — which is why this peptide has been a useful probe for asking what galanin is normally doing in a given circuit. M-15 is not selective among the three galanin receptor subtypes (GalR1, GalR2, GalR3) at the level of subtype pharmacology and is best understood as a galanin-receptor blocker in regions where the GalR1 subtype predominates, rather than a clean subtype-specific tool (Webling 2012; Freimann 2015).
Mechanism
M-15's design exploits a feature of galanin's pharmacology: the N-terminal portion of galanin (roughly residues 1–13) carries the bulk of the receptor-binding information, while the C-terminal portion contributes much less to affinity. Grafting that N-terminal recognition module onto the C-terminal heptapeptide of substance P (residues 5–11, amidated) produces a ligand that retains sub-nanomolar affinity for galanin binding sites — IC50 ≈ 0.1 nM against 125I-galanin in rat ventral hippocampus, midbrain, and spinal cord — but does not behave as a galanin agonist in functional assays in those regions (Bartfai 1991). The peptide is a reversible antagonist at the galanin binding site (Bartfai 1991). Across tissues, however, M-15's behavior is not uniform: in the rat anterior pituitary, membrane binding of M-15 is reduced compared with brain/gut tissue, which is part of the evidence that the pituitary galanin receptor is pharmacologically distinct (Wynick 1993). Subsequent cloning of three galanin receptor subtypes (GalR1, GalR2, GalR3) and their characterization with subtype-selective ligands has clarified that early M-15 results reflect the mixture of subtypes present in each tissue rather than a single defined target (Wang 1997; Lu 2005; Webling 2012).
Evidence
- Human: No human clinical trials of M-15 have been published; the peptide is a preclinical research tool.
- Animal: Reversible antagonism of galanin's inhibitory effects on hippocampal acetylcholine release in vivo and on locus coeruleus neuron firing in slices in rats (Bartfai 1991); reduced membrane binding in rat anterior pituitary used to distinguish the pituitary galanin receptor from brain/gut receptors (Wynick 1993).
- In vitro: IC50 ≈ 0.1 nM displacement of 125I-galanin in membranes from rat ventral hippocampus, midbrain, and spinal cord (Bartfai 1991); used as a reference ligand in receptor-binding and autoradiography studies across the galanin literature (Webling 2012).
Known effects
- Galanin receptor blockade in the central nervous system — Preclinical only; rat hippocampus, locus coeruleus, and spinal cord (Bartfai 1991).
- Differential binding across galanin-receptor-expressing tissues — Used to argue for receptor heterogeneity (e.g., anterior pituitary vs. brain/gut) (Wynick 1993).
- Reference antagonist in galanin pharmacology — Mechanistic and tool-compound use; not an indication (Webling 2012; Freimann 2015).
Regulatory status
- US: Not an approved drug. No FDA filing. Research-use peptide only.
- EU: No EMA approval; not marketed.
- WADA: Not listed by name; as a non-approved investigational peptide that does not fall under hormone or growth-factor categories, it has no specific prohibited-list designation known to the authoring sources.
Related peptides
- Galanin — the endogenous 29-residue (30 in humans) neuropeptide whose N-terminal 1–13 segment forms the recognition half of M-15. M-15 was built to block galanin's actions (Bartfai 1991).
- Substance P — the tachykinin neuropeptide whose C-terminal 5–11 amide segment forms the second half of M-15. Substance P's own C-terminal amide is preserved in the chimera (Langel 1992).
- Galantide (M-32) — the closely related chimera galanin-(1-12)-Pro-substance P-(5-11) amide; the first reported galanin antagonist and a sibling tool compound from the same design program (Langel 1992).
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.
Does M-15 hit all three galanin receptor subtypes equally, or does it favor one?
There are three galanin receptors with very different roles in the brain. If M-15 prefers one, researchers could use it to pin down which receptor drives memory loss or pain without confusing signals from the others.
Does the substance P portion of M-15 also bind the substance P receptor, on top of acting at the galanin receptor?
If M-15 acts on two pain-related receptors, some past spinal cord experiments may have credited the wrong receptor, and this dual action could be used on purpose to tackle chronic pain through two pathways at once.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.954011857509613 | boltz-2 |
| ranking score | 0.7852101922035217 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10567,
sequence = {GWTLNSAGYLLGPQQFFGLM},
target = {galr1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}