NeuralTier 4 β Preclinical only
Spadin
PE-SARAF peptide Β· TREK-1 blocker Β· sortilin-derived peptide
A naturally occurring peptide derived from the propeptide of sortilin, acting as a specific TREK-1 potassium channel blocker. Demonstrated rapid antidepressant-like effects comparable to fluoxetine in mouse models, with faster onset.
π IP injection or intranasal (animal research)π§ Lyophilised: β20 Β°C. Reconstituted: use within 24 hours. Sensitive to proteolytic degradation.
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Mechanism of Action
Binds and blocks the two-pore domain potassium channel TREK-1, which is overactive in depression and dampens serotonergic neuronal firing. TREK-1 inhibition disinhibits 5-HT neurons in the raphe nuclei, increasing serotonin neurotransmission without direct receptor agonism. Also enhances adult hippocampal neurogenesis.
Clinical Applications
- βTreatment-resistant depression (preclinical/early research)
- βRapid-onset antidepressant research (potential advantage over SSRIs)
- βAnxiety and stress resilience research (preclinical)
- βNeurogenesis promotion (preclinical)
Dosing Protocol
Recommended Dosing
No human dosing established. Mouse studies: 1β10 nmol/kg IP or intranasal. Short biological half-life (~20 min) presents delivery challenges. Human trials not yet initiated.Safety & Contraindications
Possible Side Effects
- β Unknown safety profile in humans
- β Theoretical cardiovascular effects via TREK-1 in cardiac tissue
- β Short half-life limits sustained action
Contraindications
- βAll human use outside approved clinical trials
- βConcurrent MAOI or serotonergic therapy (theoretical serotonin syndrome risk)
- βCardiac arrhythmia history
- βPregnancy and breastfeeding
Combinations & Synergies
π Not established β research interest in combining with conventional antidepressants for augmentation
π Preclinical comparison with ketamine as fast-acting antidepressant modality