AZD6280

AZD6280 is an orally active, blood-brain barrier-permeable GABA_A receptor modulator, with K_i values of 21 nM, 31 nM and 1680 nM against human receptors containing α2, α3 and α5 subtypes, respectively, and subtype-specific K_i values of < 30 nM for α2 and α3 subtypes. AZD6280 selectively potentiates GABA_A receptors containing α2/α3 subtypes with higher potency than α1/α5 subtypes, exerts no modulatory effect on receptors containing α1 subtypes, and regulates the tuberoinfundibular dopaminergic pathway. AZD6280 decreases peak saccadic velocity, increases serum and plasma prolactin levels, rescues dendritic abnormalities of cortical neurons induced by DISC1 knockdown. AZD6280 can be used in studies related to anxiety disorders^{[1][2][3][4][5][6][7]}. In Vitro:AZD6280 (1 µM) shows high binding selectivity for α1, α2, and α3 over α5-containing human recombinant GABA_A receptors, and acts as a positive modulator with preferential efficacy at α2 and α3 subtypes, while having no efficacy at α1 and minimal efficacy at α5 subtypes^[1].
AZD6280 acts as a partial, subtype-selective GABAAα2,3 receptor positive modulator with high affinity for α1, α2, and α3 subunits, low affinity for α5 subunits, and 32-34% of the maximal diazepam response at α2β3γ2 and α3β3γ2 subtypes^[3].
AZD6280 is a potent, selective GABAA α2/3 receptor modulator with a K_i < 30 nM for GABAA α2/3 subunits and low affinity for GABAA α5 subunits^[4].
AZD6280 (0.1 μM; 7 days) reverses DISC1 knockdown-induced dendritic deficits in primary cultured cortical neurons, restoring dendrite branch count, total length, and complexity to near-control levels^[6]. In Vivo:AZD6280 (1-7 mg/kg; p.o., i.v.; single dose) is well-absorbed, rapidly eliminated (mean terminal half-life ~4.2 h), and extensively metabolized in Wistar Hanover rats, with faeces (via biliary excretion) as the primary elimination route^[7].