AMPA Receptor Modulator-4, a 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (BTD), serves as an orally active positive allosteric modulator of the AMPA receptors (AMPAR PAMs). This compound is capable of crossing the blood-brain barrier and has been found to enhance cognitive performance and working memory in mice [1].

AMPA receptor modulator-4 (compound 15e) exhibits a pEC50 value of 5.66 for the calcium influx induced by 1 mM glutamate in HEK293 cells stably expressing the GluA2(Q) subunit [1]. The effective concentration of AMPA receptor modulator-4 required to double the response (EC2x) is 2.1 μM in FlipR and 1.5 μM in FDSS assays [1].

AMPA receptor modulator-4 administered intraperitoneally at a dose of 10 mg/kg increased the duration of Long-Term Potentiation (LTP) in rats [1]. Oral administration of the compound at 1 and 3 mg/kg, one hour prior to three treatment sessions, significantly enhanced cognitive abilities in CD1 mice [1]. The modulator, given via intraperitoneal injection at 0.03, 0.1, and 0.3 mg/kg, improved spontaneous alternation behavior and working memory performance in C57BL/6 mice [1]. Additionally, AMPA receptor modulator-4, at 30 and 100 mg/kg orally, exhibited anticonvulsant effects in NMRI mice [1].