Galanin: brain-calming neuropeptide (rat 1-29 form)
A natural signaling peptide released in the brain, spinal cord, and gut that quiets overactive nerve cells and may help suppress seizures; used mainly 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
Galanin (1–29) is the full-length form of galanin found in rats and most non-primate mammals — a 29-amino-acid neuropeptide released by neurons throughout the brain, spinal cord, and gut where it dampens the firing of nearby cells. It was first cloned from a rat hypothalamic cDNA library, where it appears as part of a larger 124-amino-acid precursor that also yields a separate fragment called galanin message-associated peptide, or GMAP (Kaplan 1988). The stored sequence here (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT) is the rat 29-residue form; in the precursor it carries a C-terminal glycine that is removed during maturation (Kaplan 1988), and mature galanin in most species is C-terminally amidated — that amide is not represented in the raw 1-letter sequence shown here. Galanin draws interest because its receptors sit at the intersection of seizure control, pain, mood, feeding, and insulin release, which has made the system a long-running target for neurological and metabolic drug discovery (Freimann 2015).
History
The galanin peptide and its gene were first characterized in rat hypothalamus in the late 1980s, with Kaplan and colleagues (1988) reporting the cDNA-derived structure of the 124-residue rat preprogalanin precursor. The deduced rat sequence proved to be roughly 90% identical to the previously known porcine galanin, with the small handful of differences clustered toward the C-terminus (Kaplan 1988). The receptor side of the system was filled in over the following decade: GalR1 was cloned first, GalR2 was identified as a distinct subtype (Wang 1997), and GalR3 was cloned in human and rat shortly after (Smith 1998), giving the three-receptor family that is still used today (Webling 2012).
What it does
When galanin (1–29) binds one of its three receptors (GalR1, GalR2, or GalR3), it generally turns down activity in the cell it is acting on (Webling 2012). In the central nervous system this shows up as anticonvulsant activity — galanin and galanin-receptor activation suppress seizure-like firing patterns, and the galanin system is regarded as an endogenous brake on seizures (Kapur 2011). In the periphery, the most classical action is in the pancreas, where galanin suppresses insulin release from β cells; this was historically the very first activity reported for galanin and is mediated by a pertussis-toxin-sensitive Gi/o-family G protein, specifically Gαo2 (Tang 2012). Galanin signalling has additionally been implicated in feeding, mood, learning and memory, nociception, and spinal reflexes (Tang 2012).
Mechanism
Galanin (1–29) acts at three class A GPCRs — GalR1, GalR2, and GalR3 — that differ in their G-protein coupling and tissue distribution (Webling 2012). GalR1 and GalR3 couple predominantly to inhibitory Gi/o proteins, while GalR2 has a broader coupling profile (Webling 2012). On pancreatic β cells, galanin's inhibition of glucose-stimulated insulin release was shown to operate specifically through the Gαo2 subunit of the Gi/o family, identified by genetic loss-of-function in mice (Tang 2012). At GalR3, the N-terminal fragment galanin (2–11) — a tool ligand often used as a putative GalR3-preferring probe — was shown in transfected cell lines to bind GalR3 with affinity comparable to full-length galanin, but with limitations as a clean subtype-selective probe (Lu 2005). The N-terminal portion of galanin (roughly residues 1–16) is generally the region required for high-affinity receptor binding across the family (Webling 2012).
Evidence
- Human: No human clinical trials of galanin (1–29) itself are documented in the dossier; clinical interest has focused on subtype-selective small-molecule and peptide analogs rather than the native 29-mer (Freimann 2015).
- Animal: Anticonvulsant effects of galanin and galanin-receptor agonists in rodent seizure models underpin the seizure-modulation literature (Kapur 2011). Inhibition of insulin release by galanin has been demonstrated in mouse pancreatic β cells, with Gαo2 identified as the required G-protein subunit by genetic knockout (Tang 2012). GalR2-preferring analogs derived from the galanin scaffold (e.g., NAX 810-2) have shown analgesic activity in rodent pain models with preclinical safety characterization (Metcalf 2017).
- In vitro: GalR1, GalR2, and GalR3 have been cloned and pharmacologically characterized in transfected cell lines, establishing the three-receptor framework used to interpret galanin pharmacology (Wang 1997; Smith 1998; Lu 2005).
Known effects
- Seizure suppression — Preclinical (rodent models, endogenous-system pharmacology; Kapur 2011)
- Inhibition of insulin release — Preclinical, mechanism mapped to Gαo2 (Tang 2012)
- Modulation of feeding, mood, nociception, learning — Mechanistic / preclinical literature, system-level (Tang 2012; Freimann 2015)
Regulatory status
Galanin (1–29) is an endogenous neuropeptide and is not an approved drug in any jurisdiction documented in the dossier. The galanin receptor system is described in the literature as a potential therapeutic target for neurological disease, but as of the cited reviews development has been pursued mainly through subtype-selective analogs rather than the native peptide (Freimann 2015).
Related peptides
- Galanin-like peptide (GALP) — a related hypothalamic peptide that shares the galanin N-terminal region and binds galanin receptors, with documented roles in energy homeostasis and reproduction (Lawrence 2011).
- Galanin (2–11) — an N-terminal fragment used as a research tool ligand and originally proposed as GalR3-preferring, with later work showing its selectivity is limited (Lu 2005).
- NAX 810-2 — a GalR2-preferring galanin analog developed as an analgesic lead with preclinical safety characterization (Metcalf 2017).
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 galanin suppress dopamine reward circuits by physically linking to the dopamine receptor?
If galanin and dopamine receptors form a direct partnership, scientists could design molecules that calm craving circuits in addiction or psychosis without blocking dopamine everywhere in the brain, cutting unwanted movement side effects.
Could the unamidated form of rat galanin favor one receptor subtype over another?
If true, this could explain why some galanin effects differ across tissues and species, and could help drug designers make more targeted galanin-based treatments with fewer side effects.
Could cyclizing rat galanin protect it from breakdown while keeping it active?
The lysine in the SFSDKHGLT tail sits at position 25 (not 26), and bridging it all the way to the start of the peptide would loop in the binding-critical front region, so the design would need care to avoid weakening receptor activity. The broad idea of constraining the easily-degraded tail is still reasonable for making a longer-lasting galanin drug.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7257987856864929 | boltz-2 |
| ranking score | 0.7565782070159912 | 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{pep10565,
sequence = {GWTLNSAGYLLGPHAIDNHRSFSDKHGLT},
target = {galr1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}