CalcMyPeptide
NeuroprotectiveAlso known as: L-Tyrosyl-L-Arginine, Tyr-Arg, KTP

Kyotorphin

Kyotorphin (Tyr-Arg) is a fascinating endogenous neuro-dipeptide first isolated from mammalian brain tissue. Operating as a master modulator of pain and neural preservation, it commands intense interest in advanced neurology. It is heavily evaluated for its profound non-opioid analgesic properties, its ability to forcibly halt neurodegenerative disease states, and its aggressive anti-amyloid actions in Alzheimer’s models.

Reviewed by CalcMyPeptide Editorial Team
Last updated: April 2026Evidence: Low1 peer-reviewed citation

Quick Stats

Half-LifeExtremely short (rapid degradation by enzymes)
Dose Range1-10 mg ICV/intranasal (research)
FrequencyPer study protocol
Vial Sizes5 mg
BioavailabilityIntrathecal/intracerebral (in research)
Year Developed1979

Scientific Data

Molecular Formula
C15H23N5O4
Molecular Weight
337.38 g/mol
CAS Number
PubChem ID

Mechanism of Action

Kyotorphin (L-Tyrosyl-L-Arginine) is a naturally occurring neuroactive dipeptide isolated from the bovine brain in 1979 in Kyoto, Japan. It functions as an endogenous analgesic neurotransmitter/neuromodulator.

Unlike opioid peptides (endorphins/enkephalins) which bind directly to opioid receptors, Kyotorphin exerts its profound pain-relieving effects (4-5x stronger than met-enkephalin) indirectly. It stimulates the regional release of endogenous enkephalins and modulates synaptic calcium channels. Because it does not directly agonize opioid receptors, it does not produce typical opioid tolerance or physical dependence, making it a highly investigated molecule in pain biology.

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 Dose1-10 mg ICV/intranasal (research)
FrequencyPer study protocol
Half-Life~0.3 hours
Common Vial Sizes5 mg

Dosing Protocols

Research Only

Dose
N/A
Frequency
N/A
Note: Cannot cross the blood-brain barrier effectively. Research uses synthetic derivatives (like ibuprofen-kyotorphin) to achieve CNS penetration.

Body-Weight Dosing Reference

Estimated doses extrapolated from the published research range of 100010000 mcg/day (referenced to 70 kg / 154 lb). These are approximations — consult a qualified healthcare provider for personalised guidance.

WeightLowTargetHigh
120 lb(54 kg)771 mcg4243 mcg7714 mcg
140 lb(63 kg)900 mcg4950 mcg9000 mcg
160 lb(73 kg)1043 mcg5736 mcg10429 mcg
180 lb(82 kg)1171 mcg6443 mcg11714 mcg
200 lb(91 kg)1300 mcg7150 mcg13000 mcg
220 lb(100 kg)1429 mcg7857 mcg14286 mcg
250 lb(113 kg)1614 mcg8879 mcg16143 mcg

💉 For exact syringe units based on your vial concentration, use the Kyotorphin Reconstitution Calculator →

Administration

Route
Research administration only (CNS delivery required)
Timing
N/A
Fasting Required?
No — food timing not critical

Expected Timeline

Immediate
Potent non-opioid-receptor-mediated analgesia in animal models.

Who Is It For?

Endogenous Analgesia

Low

Important mechanistic discovery in neuroscience. Too unstable and BBB-impermeable for standard therapeutic use.

Reconstitution Example

Vial
5 mg
Water
1 mL
Concentration
5 mg/mL
Per Unit (100u syringe)
50 mcg
Dose of 1000 mcg = 20 units on a 100-unit insulin syringe

Safety & Considerations

Endogenous molecule. No human clinical dosing protocol exists due to blood-brain barrier permeability issues and rapid enzymatic degradation in plasma.

Regulatory & Legal Status

FDA Status (US)
Research Only
WADA Status (2026)
Not Listed

Not currently on the WADA 2026 Prohibited List. Policies may change — verify before competition.

Classification

Research Chemical

US Compounding: Not eligible / not available

⚠️ This information is for educational purposes only and may not reflect the most current regulatory updates. Always verify with official FDA, WADA, and jurisdiction-specific sources before use.

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.

Dosing Quick Reference

Kyotorphin— Dosing Guide
Dose Range
1-10 mg ICV/intranasal (research)
Half-Life
~0.3 hours
Frequency
Per study protocol
Route
Subcutaneous
5 mg vial
💧 1 mL BAC water📐 5 mg/mL concentration💉 50 mcg/unit (100u syringe)
Neuroprotectivecalcmypeptide.com

Frequently Asked Questions

Is Kyotorphin an opioid?
No, but it acts on the pain system. It does not bind to opioid receptors; instead, it causes your brain to release its own stored enkephalins (natural painkillers).

References

  1. Takagi H et al. "Isolation and structure of a new analgesic dipeptide (kyotorphin) from bovine brain".” Nature (1979). PMID: 512406

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