TAK-653 (osavampator, Neurocrine code NBI-1065845) is an oral AMPA receptor positive allosteric modulator discovered by Takeda.
Amounts reported for TAK-653 are listed under Reported protocols, each with its source and study kind. No amount ladder is inferred from them. This is educational source context, not a protocol or recommendation.
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What published studies and recent community write-ups report about amounts, timing and course length. 2 clinical, 2 preclinical and 1 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Clinical2 rows | |||||
| Phase 2 SAVITRI trial in major depressive disorder183 adults aged 18-65 with major depressive disorder and an inadequate response to antidepressant treatment, randomised 2:1:1 to placebo, 1 mg or 3 mg (NCT05203341) | 1 mg or 3 mg | Once daily | Oral tablets, added to existing antidepressant treatment | 8 weeksNone described | Neurocrine Biosciences via PR Newswire (company press release)2025 |
| The 1 mg dose beat placebo on the MADRS depression scale by 4.3 points at day 28 and 7.5 points at day 56 and significantly improved response and remission rates at day 56, while 3 mg showed only non-significant trends. No serious adverse events occurred; headache and nasopharyngitis were the most common complaints and were similar to placebo. These figures come from a company press release and congress poster rather than a peer-reviewed paper, and an exposure-response analysis led Neurocrine to carry 1 mg once daily into phase 3. | |||||
| Pharmacodynamic crossover study in healthy volunteers24 healthy volunteers in a randomised, double-blind, placebo-controlled three-way crossover | 0.5 mg and 6 mg | Single doses, one per study period | Oral | Single doses with NeuroCart testing at 3.5 and 4 hoursWashout between periods | Translational Psychiatry (PubMed Central)2022 |
| Neither dose changed body sway or subjective drug effects, but 0.5 mg increased saccadic peak velocity and altered Stroop performance and 6 mg improved adaptive tracking and smooth pursuit, a pattern the authors call psychostimulant-like and consistent with the increased cortical excitability seen earlier with transcranial magnetic stimulation. Several authors were Takeda employees. | |||||
| Preclinical2 rows | |||||
| Cognition and seizure margin in rodentsRats in the novel object recognition test; mice for hippocampal BDNF expression | 0.03, 0.1 and 0.3 mg/kg (recognition memory in rats); 3 and 10 mg/kg (BDNF mRNA in mice) | Single doses | Oral | Single-dose experimentsNot applicable | Scientific Reports (PubMed Central)2021 |
| TAK-653 improved recognition memory in rats from 0.03 mg/kg and working memory in further tests, while the agonist-like potentiator LY451646 improved only recognition memory and caused seizures at 10-30 mg/kg. TAK-653 raised hippocampal BDNF only when AMPA was co-administered, which the Takeda authors use to argue that it works solely by amplifying glutamate that is already released, and it showed a 419-fold plasma Cmax margin against convulsion in rats. | |||||
| Antidepressant-like effect in ratsRats in the reduction of submissive behaviour model, with ketamine 30 mg/kg as the comparator | Sub-chronic course over 6 days (dose levels are not given in the abstract) | Daily for 6 days | Not stated in the abstract | 6 daysNot applicable | Pharmacology, Biochemistry and Behavior (PubMed)2021 |
| Six days of TAK-653 produced an antidepressant-like effect comparable to ketamine, whose own effect was blocked by the AMPA antagonist NBQX, and unlike ketamine TAK-653 did not cause hyperlocomotion, the rat proxy for psychotomimetic effects. In cultured cortical neurons it activated mTOR, Akt and ERK signalling and raised BDNF protein. This is a Takeda in-house study. | |||||
| Community-reported1 row | |||||
| Vendor tablet format | 2 mg per tablet, 60 tablets per bottle (120 mg total); no dose stated | Not stated | Oral | Not statedNot stated | Community resource2026 |
| A vendor claim. The 2 mg tablet is twice the 1 mg dose that worked in the phase 2 trial and below the 3 mg dose that did not reach significance; the product page lists Takeda and Neurocrine papers but gives no amount per administration, and the certificate for lot TK01 records identity by mass spectrometry without a measured content. The compound was out of stock when this page was read. | |||||
Plus 1 community resource (a dosing guide, forum thread or vendor write-up), reported above but not linked.
TAK-653 (osavampator, Neurocrine code NBI-1065845) is an oral AMPA receptor positive allosteric modulator discovered by Takeda and designed to amplify glutamate signalling while having almost no agonist activity of its own, which in rats gave it a several-hundred-fold margin against seizures. Neurocrine Biosciences licensed it in 2020, and in the phase 2 SAVITRI trial of 183 adults with major depressive disorder and an inadequate response to antidepressants, 1 mg once daily for eight weeks lowered depression scores significantly more than placebo while 3 mg did not reach significance. A five-study phase 3 programme began in January 2025 with topline data expected in 2027; the compound is not approved anywhere and is sold online as 2 mg tablets.
These themes describe recurring questions in published research. They are not claims of effectiveness or recommendations for use.
Neuroplasticity, cognition, stress and sleep models.
The 1 mg dose beat placebo on the MADRS depression scale by 4.3 points at day 28 and 7.5 points at day 56 and significantly improved response and remission rates at day 56, while 3 mg showed only non-significant.
Neither dose changed body sway or subjective drug effects, but 0.5 mg increased saccadic peak velocity and altered Stroop performance and 6 mg improved adaptive tracking and smooth pursuit, a pattern the authors call.
TAK-653 improved recognition memory in rats from 0.03 mg/kg and working memory in further tests, while the agonist-like potentiator LY451646 improved only recognition memory and caused seizures at 10-30 mg/kg. TAK-653.
Six days of TAK-653 produced an antidepressant-like effect comparable to ketamine, whose own effect was blocked by the AMPA antagonist NBQX, and unlike ketamine TAK-653 did not cause hyperlocomotion, the rat proxy for.
A vendor claim. The 2 mg tablet is twice the 1 mg dose that worked in the phase 2 trial and below the 3 mg dose that did not reach significance; the product page lists Takeda and Neurocrine papers but gives no amount.
Study models remain visible so laboratory and animal findings are not mistaken for established human outcomes.
2 protocol rows on this page come from human trials, trial registrations, regulator labels or reviews of human data. Approval status and populations are stated per row.
2 protocol rows describe animal, cell or toxicology work. Amounts from these rows do not translate to people.
1 row record what blogs, vendor write-ups or forums describe for TAK-653. None has been verified against primary literature.
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
Osavampator, TAK-653, NBI-1065845, Osavampator [INN], UNII 9E3TOE5RIZ, CHEMBL4594403
PXJBHEHFVQVDDS-UHFFFAOYSA-N
9-(4-cyclohexyloxyphenyl)-7-methyl-3,4-dihydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide
8 curated references, each with its journal, year and study model, plus 1 community resource reported but not linked.