Spadin
Sortilin propeptide antidepressant · NTSR3/sortilin propeptide fragment · Spadin peptide
A naturally occurring antidepressant peptide derived from the pro-peptide of the sortilin receptor, which blocks TREK-1 (a background K+ channel) to produce rapid antidepressant effects in preclinical models.
Half-Life
~minutes in plasma (rapidly degraded by serum proteases); mini-spadin analogs show improved stability
MW
~2100 Da (17 AA)
Amino Acids
17 AA
Evidence
Preclinical
Regulatory Status
Research chemical. No clinical trials initiated yet. Preclinical antidepressant activity well-established in rodent models. Short serum half-life of native spadin requires development of stable analogs for clinical translation. No FDA/EMA status.
In Plain English
A naturally occurring piece of a brain protein that works as a rapid-acting antidepressant by releasing the brake on serotonin neurons. Spadin blocks a potassium channel (TREK-1) that normally keeps serotonin neurons quiet — blocking it lets them fire more freely, boosting serotonin without the 2-6 week delay of SSRIs. Discovered by accident when researchers noticed TREK-1 knockout mice seemed impossible to depress.
Overview
Spadin is a 17-amino acid peptide (and its shorter analog mini-spadin, 4 AA) derived from the signal propeptide of sortilin, a receptor involved in BDNF processing and neurotrophin sorting. Spadin was identified as an endogenous blocker of TREK-1 (TWIK-related K+ channel 1), a two-pore domain background potassium channel constitutively expressed in neurons. TREK-1 is unique: it is the only ion channel whose knockout in mice produces an antidepressant phenotype. By blocking TREK-1, spadin mimics the effects of TREK-1 ablation, enhancing serotonergic neurotransmission and producing antidepressant-like effects in animal models with notably rapid onset (within 24-48 hours versus the weeks typical of SSRIs). Spadin represents a novel antidepressant mechanism entirely distinct from monoamine reuptake inhibitors, MAO inhibitors, or ketamine/NMDA pathway drugs.
Common Formats
- Research-grade synthetic peptide (SC/IP in animal research)
- Mini-spadin (4 AA) analog studied for improved stability
Storage Notes
Lyophilized: -20°C long-term, -80°C for extended storage. Reconstituted in sterile PBS: 4°C, 1-2 weeks. Minimize freeze-thaw cycles.
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Related Compounds
Selank
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Semax
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DSIP
A naturally occurring neuropeptide that regulates sleep-wake cycles, stress response, and has shown longevity-associated effects in animal research.
PE-22-28
Synthetic octapeptide fragment of spadin that blocks TREK-1 potassium channels, producing rapid antidepressant and cognitive effects in preclinical models.
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