Kyotorphin
Endogenous dipeptide (Tyr-Arg) discovered in bovine brain — releases met-enkephalin, produces analgesia, and demonstrates neuroprotective and anti-amyloid properties in preclinical models.
🔬 Mechanism of Action
Kyotorphin (L-Tyr-L-Arg) is an endogenous analgesic dipeptide originally isolated from bovine brain in 1979 by Takagi et al. at Kyoto University. It exerts its analgesic effects primarily by stimulating the release of Met-enkephalin from spinal cord and brain neurons, effectively activating the endogenous opioid system without directly binding opioid receptors. Kyotorphin also inhibits DPP-III (dipeptidyl peptidase III), the primary enzyme that degrades enkephalins, thereby amplifying endogenous analgesia. Recent research demonstrates neuroprotective properties: Kyotorphin reduces amyloid-β aggregation in neuronal cell cultures and modulates NMDA receptor activity, suggesting potential applications in Alzheimer disease research.
Source: PMID: 3427544
📜Background & History
Kyotorphin was discovered in 1979 by Hiroshi Takagi at Kyoto University during a systematic search for endogenous analgesic substances in bovine brain. It was the first non-opioid endogenous analgesic dipeptide identified. Recent decades have expanded interest beyond analgesia to neuroprotection: Kyotorphin derivatives show promise in reducing amyloid-β neurotoxicity and modulating glutamatergic transmission, making it a candidate for Alzheimer disease research.
🎯 Research Use Cases
- ✓Endogenous analgesia research
- ✓Neuroprotection research
- ✓Alzheimer disease research
- ✓NMDA receptor modulation
💉 Dosing Protocol
| Typical Dose | 1-10 mg ICV/intranasal (research) |
| Frequency | Per study protocol |
| Half-Life | ~0.3 hours |
| Common Vial Sizes | 5 mg |
🧪 Reconstitution Example
⚠️Safety & Considerations
Endogenous molecule with expected safety at physiological concentrations. Blood-brain barrier penetration is limited for exogenous administration — intranasal and amidated derivatives are under investigation. Research-only compound.
⚡Interactions & Contraindications
Research compound. May potentiate effects of opioid analgesics through enkephalin amplification. Theoretical interaction with NMDA modulators.
🔗Synergies & Common Stacks
Kyotorphin (enkephalin release) + Selank (anxiolytic tuftsin analogue) — both modulate endogenous opioid and enkephalin systems through complementary mechanisms.
Kyotorphin + Semax for dual neuroprotective approach: Kyotorphin via enkephalin/NMDA modulation, Semax via BDNF expression.