Montirelin
A metabolically stable copy of the brain tripeptide TRH, developed in Japan to rouse the brain — against cataplexy, impaired consciousness and memory loss — that did not reach approval
Thyrotropin-releasing hormone (TRH) is a three-amino-acid brain peptide with a second life, beyond its thyroid job, as a general arousal and protective signal. Montirelin (NS-3, CG-3703) is a Japanese analogue built to keep those brain actions while lasting far longer than TRH, whose effect is gone in minutes. In animals it reduced the sudden muscle collapse of narcolepsy (cataplexy), improved disturbed consciousness after brain injury, and reversed drug-induced memory loss. It carried a full preclinical and toxicology package and reached early clinical testing, but it was not developed to approval and is not a marketed medicine.
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What is it?
TRH is best known for sitting at the top of the thyroid axis, but injected into the brain it does something else: it raises arousal, counters sedation and protects nerve cells. Those central actions made TRH and its analogues candidates for conditions of too little arousal — impaired consciousness after brain injury, the excessive sleepiness and sudden muscle collapse (cataplexy) of narcolepsy, and the fog of dementia. The drawback is that TRH itself is destroyed within minutes and carries an unwanted thyroid effect.
Montirelin, coded NS-3 and CG-3703 by Nippon Shinyaku, is a Japanese analogue that replaces TRH's front residue with a sulphur-containing ring, making it metabolically stable and favouring the brain actions. Its most striking results were in narcolepsy. Dogs with naturally occurring narcolepsy are a standard model, and in them the drug reduced cataplexy and daytime sleep in a dose-dependent way, and stayed effective when taken by mouth over two weeks, which matters for a chronic condition.
Its other main line was acute brain states. In rats it reversed the memory disruption caused by scopolamine, a drug used to model the cholinergic failure of dementia, and separate work traced that to the drug boosting the release of acetylcholine and noradrenaline in the brain. In models of impaired consciousness it acted as an analeptic, a brain-rousing agent, and in spontaneously epileptic rats chronic treatment reduced seizures.
A pharmacokinetic study in rats, dogs and monkeys documented how the drug was handled after injection, and the published Japanese record includes a full regulatory toxicology package: single- and repeat-dose toxicity in several species, reproductive and developmental studies, mutagenicity and antigenicity testing. That depth of preclinical work is a sign the molecule was taken seriously as a drug candidate.
Montirelin reached early clinical testing but was not brought to approval, and its development did not continue. No study of montirelin in people is published in PubMed, so its whole published record is the preclinical work. Of the many TRH analogues, taltirelin reached approval in Japan for spinocerebellar degeneration; montirelin, like most, did not. It is of research interest only, is not a medicine, and nothing here is a dose to use.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Mechanism of Action
Montirelin is a sturdier copy of TRH aimed at TRH's brain-rousing and protective actions. It works through the same neurotransmitter systems TRH influences rather than one single target.
TRH's central arousal actions
TRH raises arousal and counters sedation in the brain, separate from its thyroid role. Montirelin reproduces these as a metabolically stable analogue (FDA GSRS UNII 30MUJ6YYUY), acting as an analeptic against impaired consciousness and cataplexy (PMIDs 10869884, 9236248).
Acetylcholine and noradrenaline
Its reversal of scopolamine-induced memory loss was linked to increased release of acetylcholine and noradrenaline in the brain (PMID 7675879), the transmitter systems TRH analogues act through.
A ring that makes it last
Replacing TRH's N-terminal pyroglutamyl with a methyl-oxo-thiomorpholinyl ring (FDA GSRS UNII 30MUJ6YYUY) resists the enzymes that clear TRH in minutes, giving a longer-acting, orally active drug (PMID 10869884).
Published Research
These are studies of montirelin read from their PubMed abstracts on November 5, 2026. The published record is preclinical: narcolepsy in dogs, memory and seizure models in rats, and pharmacokinetics across species, alongside a Japanese toxicology package. No human study of montirelin is indexed in PubMed, though the molecule reached phase 2.
Oral treatment of canine narcolepsy
In dogs with naturally occurring narcolepsy, oral montirelin (as CG-3703) reduced cataplexy across 0.25 to 16 milligrams per kilogram and reduced daytime sleep at 8 and 16 mg/kg, both dose-dependently, and a two-week course at 16 mg/kg kept working. Showing the drug was orally active and did not lose effect with repeated dosing mattered for a chronic disease like narcolepsy.
TRH analogues against cataplexy in dogs
Using the canine narcolepsy model, the study compared TRH with the stable analogues CG3703 (montirelin), CG3509 and TA0910 on daytime sleep and cataplexy. The analogues reduced the narcoleptic symptoms, supporting the idea that TRH-type compounds could treat the excessive sleepiness and muscle collapse of narcolepsy.
Reversing drug-induced memory loss in rats
In rats, montirelin (NS-3, CG3703) at 0.3 milligrams per kilogram reversed the memory disruption caused by scopolamine in maze tasks, including a delayed non-matching-to-sample test. Scopolamine is used to model the loss of acetylcholine signalling seen in dementia, so the result pointed to a cognition-protecting action.
Seizures in epileptic rats
Spontaneously epileptic rats, a strain that has both tonic and absence-like seizures, were given the TRH analogue CNK-602A (montirelin) long-term. The study examined whether chronic treatment, not just single doses, could control the seizures, extending the drug's central actions to epilepsy.
Pharmacokinetics across species
The plasma levels, metabolism and excretion of radiolabelled montirelin were measured in rats, dogs and monkeys after single intravenous doses of 0.25, 1 and 4 milligrams per kilogram. Exposure rose with dose; the study is part of the pharmacokinetic and toxicology package assembled during the drug's development.
Side Effects & Contraindications
Reported Side Effects
From preclinical studies only; there is no human safety record for montirelin in PubMed.
Contraindications & Cautions
Montirelin has no label and no approved use. These points come from its class and the preclinical work.
Legal Status
Montirelin is an investigational compound that was never approved in any country and is not marketed.
Frequently Asked Questions
?What is montirelin?
An experimental drug from Japan, coded NS-3 and CG-3703, that is a longer-acting, metabolically stable copy of the brain tripeptide TRH (thyrotropin-releasing hormone). It was studied to rouse the brain — against narcolepsy, impaired consciousness and memory loss.
?Was it ever approved?
No. Montirelin reached early clinical testing (ChEMBL records phase 2) but was not developed further and was never approved or marketed anywhere.
?What was it studied for?
Mainly narcolepsy: in dogs with narcolepsy it reduced cataplexy and daytime sleep, and worked by mouth (PMIDs 10869884, 9236248). It also reversed drug-induced memory loss in rats and reduced seizures in epileptic rats.
?Is there human evidence?
Not in the published literature indexed by PubMed, which is all animal and laboratory work plus a toxicology package. ChEMBL shows it reached phase 2, but no human study of montirelin is indexed, so this page describes the preclinical evidence only.
?Is it available to buy?
No. Montirelin is not a medicine and is not sold as one. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [animal] Riehl J, et al. "Chronic oral administration of CG-3703, a thyrotropin releasing hormone analog, increases wake and decreases cataplexy in canine narcolepsy." Neuropsychopharmacology, 2000;23(1):34-45. PMID: 10869884.
- [animal] Nishino S, et al. "Effects of thyrotropin-releasing hormone and its analogs on daytime sleepiness and cataplexy in canine narcolepsy." J Neurosci, 1997;17(16):6401-8. PMID: 9236248.
- [animal] Ogasawara T, et al. "NS-3(CG3703), a TRH analog, ameliorates scopolamine-induced memory disruption in rats." Pharmacol Biochem Behav, 1995;51(4):929-34. PMID: 7675879.
- [animal] Momiyama T, et al. "Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats." Epilepsia, 1996;37(4):328-31. PMID: 8603636.
- [animal] Sugimoto T, et al. "Pharmacokinetics of the new thyrotropin releasing hormone analogue montirelin hydrate. 1st communication: plasma concentrations, metabolism and excretion after a single intravenous administration to rats, dogs and monkeys." Arzneimittelforschung, 1996;46(2):106-13. PMID: 8720298.
- [other] FDA Global Substance Registration System, Montirelin, UNII 30MUJ6YYUY (tetrahydrate 27MN0584ML; INN 6190, CAS 90243-66-6, PubChem 6917793; codes NS-3, CG-3703, CNK-602A), read November 5, 2026: a thyrotropin-releasing hormone analogue, N-[[(3R,6R)-6-methyl-5-oxo-3-thiomorpholinyl]carbonyl]-L-histidyl-L-prolinamide. https://gsrs.ncats.nih.gov/ginas/app/beta/substances/30MUJ6YYUY
- [other] ChEMBL molecule CHEMBL2304039 (MONTIRELIN), read November 5, 2026: synonyms Montirelin, Montirelina, NS-3, CG-3703, CNK-602A; highest clinical phase recorded 2, no first approval. https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL2304039/
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 5, 2026: no application and no label record for montirelin. It has an FDA substance record (UNII 30MUJ6YYUY) and an INN.
- [registry] ClinicalTrials.gov API v2, searched November 5, 2026: 0 records for montirelin, NS-3 or CG-3703 as this molecule. Its development in Japan predates and sits outside the registry. https://clinicaltrials.gov/search?term=montirelin
Sources & Citations
The five preclinical studies carded above were read from their PubMed records on November 5, 2026. Structure, codes and identifiers come from the FDA Global Substance Registration System (UNII 30MUJ6YYUY) and ChEMBL (CHEMBL2304039); the absence of approval from Drugs@FDA and openFDA, and of registered trials from ClinicalTrials.gov, all checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.