Neuroprotective

Kyotorphin

L-Tyrosyl-L-Arginine · Tyr-Arg · KTP

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.

Not FDA-approved - research chemical

Reviewed by CalcMyPeptide Editorial Team

·Last updated: August 2026·Evidence: Low·1 peer-reviewed citation

Typical research dose

1-10 mg ICV/intranasal (research)

Frequency

Per study protocol

Half-life

Extremely short (rapid degradation by enzymes)

Common vials

5 mg

CAS

70904-56-2

Molecular weight

337.38 g/mol

Use-case scores

0–10 against the evidence we have, not a gym ranking. Hidden domains do not apply here.

Injury & tissue2/10
Historical analgesic dipeptide. Not a pain NDA. Mechanism/in vitro band.

Compound card

Class: Tyr-Arg dipeptide (endogenous analgesic research)
Formula: C15H23N5O4
Status: Not FDA-approved · research use

Dose it

5 mg + 1 mL BAC water → 5 mg/mL · 1000 mcg ≈ 20 units (U-100)

Open in calculator

How it works

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

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

Administration

Route / form

Research administration only (CNS delivery required)

Timing

N/A

Empty stomach?

No - Food timing is not critical.

Timeline

Immediate

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

Who it is for

Endogenous Analgesia

Low

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

Reconstitution

Vial	Water	Concentration	Example dose
5 mg lyophilized	1 mL BAC	5 mg/mL	Research dipeptide. No labeled dose.

Change vial size or water volume? Open the reconstitution calculator.

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.

Limits of current evidence

This site will not treat pain from a kyotorphin page.

Verdict

Kyotorphin is Tyr-Arg. Opioid-adjacent folklore from the 1970s. Not morphine and not a research-chem pain protocol.

Interactions & Contraindications

Research compound. May potentiate effects of opioid analgesics through enkephalin amplification. Theoretical interaction with NMDA modulators.

Synergies & Common Stacks

+ Selank →

Kyotorphin (enkephalin release) + Selank (anxiolytic tuftsin analogue) - both modulate endogenous opioid and enkephalin systems through complementary mechanisms.

+ Semax →

Kyotorphin + Semax for dual neuroprotective approach: Kyotorphin via enkephalin/NMDA modulation, Semax via BDNF expression.

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

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

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