TAK-137

TAK-137 belongs to small molecule compounds, acting as a positive allosteric modulator of AMPA receptors, with favorable brain penetration and oral activity. Suitable for research on depression and cognitive impairment associated with schizophrenia.

Methods: In GluA1i CHO cells and primary rat neurons, TAK-137 (1 nM–30 μM) was used for Ca2+ influx assays and whole-cell patch-clamp recordings.
Results: TAK-137 induced Ca2+ influx and AMPA receptor currents only in the presence of agonists, with no intrinsic agonist activity, whereas LY451646 activated receptors even in the absence of agonists. [1]

Methods: In Sprague-Dawley rats, ICR mice, and cynomolgus monkeys, TAK-137 (dissolved in 0.5% methylcellulose) was administered orally for novel object recognition, DMTS tasks, neural progenitor cell proliferation, and seizure observation.
Results: TAK-137 (0.03–1 mg/kg) improved cognition in monkeys; 0.1–3 mg/kg promoted neurogenesis in rodents; seizure safety window was 116-fold for AUCbrain in rats and >49-fold for AUCplasma in monkeys. [1]
Methods: In rat primary hippocampal neurons, whole-cell patch-clamp recordings were performed to assess the effect of TAK-137 (0.1–30 μM) on AMPA-evoked currents.
Results: TAK-137 concentration-dependently enhanced AMPA currents (EC50 = 1.4 μM) with an enhancement magnitude of 7127-fold; at 30 μM, baseline current was only slightly affected, far less potent than the strong agonist effect of LY451646. [2]