Galanin
GAL, galanin(1-30), GMAP precursor peptide
Galanin is a neuropeptide widely distributed in the brain, spinal cord and gut, notable because the human form is 30 residues and lacks the C-terminal amide found in every other species examined. It acts at three receptors regulating seizure threshold, mood, nociception, feeding and nerve regeneration. Despite an unusually clean preclinical anticonvulsant story, no galanin-based drug has entered human trials.
Mechanism
Galanin is cleaved from preprogalanin, which also yields galanin message-associated peptide. The N-terminal residues 1 to 14 are near-identical across mammals, birds, reptiles, amphibians and fish, and carry receptor binding; the divergent C-terminus explains why human galanin behaves differently in some assays. Three receptors are known. GAL1 and GAL3 couple to Gi/Go, inhibiting adenylate cyclase and opening G protein-coupled inwardly rectifying potassium channels, producing neuronal hyperpolarisation. GAL2 couples predominantly to Gq/11 with phospholipase C activation and calcium mobilisation, and is the receptor most associated with neuroprotection, neurogenesis and anticonvulsant effects.
Galanin is co-stored with noradrenaline in the locus coeruleus, with acetylcholine in basal forebrain cholinergic neurons, and with serotonin in the dorsal raphe. Its release is markedly increased by high-frequency firing, so it acts as a state-dependent brake on monoaminergic and cholinergic tone. Expression is dramatically upregulated in dorsal root ganglia after nerve injury and in hippocampus after seizures, consistent with an endogenous compensatory role.
What the research shows
The strongest data are anticonvulsant. Galanin and engineered analogues suppress seizures in the Frings audiogenic mouse, corneal kindling and the 6 Hz model of pharmacoresistant partial seizures, and galanin knockout animals show lowered seizure threshold with impaired seizure termination. NAX 5055, a systemically bioavailable galanin analogue, retained low nanomolar receptor affinity and was active across all three models.
What is missing is any human evidence at all. NAX 5055 was flagged in 2009 as requiring long-term toxicity and tolerance work before clinical development, and no galanin receptor ligand has since reached the clinic. Human data are confined to observational measurements of galanin in cerebrospinal fluid, plasma and post-mortem tissue in depression, Alzheimer's disease, epilepsy and pituitary tumours, none of which establish causation or therapeutic value.
Evidence assessment
Preclinical only
Every citation that survived audit is either a foundational isolation paper, a rodent pharmacology study or a nomenclature review. No galanin peptide or galanin receptor ligand has completed, or to our knowledge entered, a human clinical trial. There is no human efficacy or safety evidence of any kind.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Galanin - a novel biologically active peptide from porcine intestine Preclinical only
Original isolation and sequencing of galanin, named for its N-terminal glycine and C-terminal alanine in the porcine form.
Developing novel antiepileptic drugs: characterization of NAX 5055, a systemically-active galanin analog, in epilepsy models Preclinical only
NAX 5055 retained low nanomolar galanin receptor affinity and was active in Frings audiogenic, corneal kindled and 6 Hz pharmacoresistant seizure models. Rodent data only.
Galanin receptors: IUPHAR/BPS Guide to Pharmacology classification Preclinical only
Defines GAL1, GAL2 and GAL3 signalling and confirms human galanin as a 30-residue non-amidated peptide, distinct from the 29-residue amidated forms in other species.
Safety
There is no human safety database. Peptide galanin is not used in people. Predicted risks from the biology include sedation, cognitive impairment through cholinergic inhibition, hypotension and effects on glucose handling, since galanin inhibits insulin release in several species. Any product sold as galanin for human use is unregulated and untested.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No UK marketing authorisation. Unlicensed substance with no legitimate supply route for human consumption. |
| United States | No FDA approval and no galanin-based product in clinical development. Supplied only as a research reagent, explicitly not for human use. |
| WADA (sport) | Not individually named on the WADA Prohibited List but captured by section S0 as a pharmacological substance with no regulatory approval for human therapeutic use, prohibited at all times. |
Questions
Not as a therapy. There are no completed clinical trials of galanin or any galanin receptor drug. Human work is limited to measuring the peptide in blood, cerebrospinal fluid and post-mortem tissue.
Human galanin is 30 amino acids and lacks the C-terminal amide that porcine, rat and other galanins carry on 29 residues. It also has glycine at position 17 where porcine galanin has aspartic acid. This matters when interpreting rodent data.