data + articles · 2 listed
newest 2019spec sheet8 rows
TAK-137; the preclinical low-agonism AMPA receptor potentiator that pioneered the wide-seizure-margin design later carried into the clinical lead TAK-653, with strong procognitive animal data but no human efficacy program.
- established the low-agonism AMPA-PAM design (Ser743 interference) later carried into the clinical lead TAK-653
- broad preclinical procognitive effects: attention, working memory and cognitive flexibility in rats and monkeys
- wider seizure safety margin than the older ampakine LY451646
- induces BDNF and promotes neural progenitor proliferation in preclinical models
Overview
the preclinical sibling of TAK-653; a low-agonism AMPA potentiator with strong procognitive animal data and a wide seizure margin, but no human efficacy program. it is the science that made TAK-653 possible.
- it and TAK-653 are chemical cousins built on the exact same low-agonism idea.
- the whole trick is one contact point, Ser743, that keeps the drug from over-activating the receptor.
- it improved working memory even in monkeys whose cognition had been impaired by ketamine.
- it never went into human efficacy trials; its clinical torch was carried by TAK-653.
Mechanism
TAK-137 (9-(4-phenoxyphenyl)-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide) is a positive modulator of the subtype of receptors with deliberately minimal intrinsic activity, and it is the direct preclinical forerunner of TAK-653. according to PubMed, Takeda showed that structural interference at Ser743 on the is the key to lowering the agonistic effect of this dihydropyridothiadiazine-dioxide scaffold; TAK-137 potentiated glutamate signaling with a lower agonistic effect than the reference potentiator LY451646, induced in neurons, and improved cognition in both rats and monkeys, while showing a wider safety margin against seizures and enhancing neural progenitor proliferation over a broad dose range (Kunugi et al., 2018, Neuropsychopharmacology, https://doi.org/10.1038/s41386-018-0213-7). in a dedicated schizophrenia-focused characterization, TAK-137 partially inhibited stimulant- and MK-801-induced hyperlocomotion (weak effect on positive-symptom models), ameliorated MK-801-induced social-interaction deficits (a negative-symptom model), and improved multiple cognitive domains: attention in the five-choice serial reaction time task, working memory in the radial arm maze and in ketamine-treated monkeys' delayed matching-to-sample task, and cognitive flexibility in phencyclidine-treated rats' reversal learning (Tanaka et al., 2019, Pharmacol Res Perspect, https://doi.org/10.1002/prp2.479). the practical significance is that TAK-137 established the low-agonism/wide-window concept that carried over into TAK-653; the two share mechanism and scaffold, but TAK-137 remained a preclinical schizophrenia-cognition tool while TAK-653 became the human clinical lead. there is no published human efficacy data for TAK-137 itself, so its evidence base is entirely preclinical.
receptor fingerprint
(positive site)positive allosteric modulator with low intrinsic agonism; potentiates glutamate-evoked signaling
GluA1 Ser743 (structural interaction site)structural interference at Ser743 lowers the agonistic effect of the dihydropyridothiadiazine-dioxide scaffold
/ neural progenitor proliferation (downstream)induces BDNF and promotes neural progenitor proliferation over a broad dose range
Safetyrisks and cautions, not medical advice
safety information is preclinical. as an AMPA potentiator its defining liability is seizure risk; TAK-137 was engineered to widen that margin relative to older ampakines, but the concern is intrinsic to the class. there is no human safety database and no established dose. it is a research compound, not a medicine or supplement, and should not be sourced or self-administered.
History
TAK-137 came out of Takeda's effort to solve the two chronic problems of AMPA potentiators, bell-shaped dosing and seizures, by minimizing intrinsic agonism. its 2018-2019 characterization demonstrated the low-agonism concept and strong procognitive effects in schizophrenia-relevant animal models, and it directly seeded the design of TAK-653, which became the clinical candidate. TAK-137 itself did not advance into a public human efficacy program.
Reputation
in the glutamatergic-cognition literature TAK-137 is respected as the elegant preclinical proof-of-concept behind the low-agonism ampakine strategy; the compound that showed you could get robust procognitive effects with a wide seizure margin. it is less famous than TAK-653 because it stayed in the lab, but it is frequently cited as the mechanistic groundwork for it.
Subjective profileweighing the evidence above
A design milestone rather than a usable compound: it proved a low-agonism AMPA potentiator could widen the seizure margin, and that work carried forward into TAK-653. Seizure risk is intrinsic to the class, there is no human safety database and no established dose, so this is not something to source.
Resources
This entry is here for reference.
Research
- 1.TAK-137, an AMPA-R potentiator with little agonistic effect, has a wide therapeutic window
- 2.Preclinical characterization of AMPA receptor potentiator TAK-137 as a therapeutic drug for schizophrenia
2 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
what is TAK-137?
it is an AMPA receptor potentiator (an ampakine) from Takeda with deliberately low intrinsic agonism. it is the direct preclinical sibling of TAK-653; both use the same design idea of amplifying real glutamate signaling without over-activating receptors, which keeps the seizure risk down (Kunugi et al., 2018, Neuropsychopharmacology, https://doi.org/10.1038/s41386-018-0213-7).
how is it different from TAK-653?
they are close chemical relatives on the same dihydropyridothiadiazine-dioxide scaffold and share the low-agonism, Ser743-interference mechanism. TAK-137 was explored mainly for schizophrenia-related cognition in animals, while TAK-653 became the clinical lead that advanced into human depression trials. think of TAK-137 as the proof-of-concept and TAK-653 as the one taken forward.
does it improve cognition?
in animals, yes, fairly robustly. TAK-137 improved attention, working memory and cognitive flexibility across rats and monkeys, including reversing MK-801- and ketamine-induced deficits, at low oral doses (Tanaka et al., 2019, Pharmacol Res Perspect, https://doi.org/10.1002/prp2.479; Kunugi et al., 2018, Neuropsychopharmacology, https://doi.org/10.1038/s41386-018-0213-7). these are preclinical results, not human data.
what about the seizure risk that plagues ampakines?
TAK-137 was specifically shown to have a wider safety margin against seizure than the older potentiator LY451646, thanks to its low agonistic activity; it also enhanced neural progenitor proliferation over a broader dose range (Kunugi et al., 2018, Neuropsychopharmacology, https://doi.org/10.1038/s41386-018-0213-7). still, seizure liability is the defining concern for the class.
was it ever tested in people?
there is no published human efficacy program for TAK-137; the substantive record is preclinical. Takeda's clinical development effort in this AMPA-PAM series centered on TAK-653. so TAK-137 is best understood as an important research compound rather than a clinical drug.
can i buy it as a nootropic?
no. it is a preclinical research compound with no approved use, no established human dose, and real seizure considerations for its drug class. it is documented here to explain the science behind the more advanced TAK-653.