AZD7325

AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (K_i=0.3 and 1.3 nM, respectively), and has less antagonistic efficacy at the Aα1?and Aα5?receptor subtypes^[1][4]. AZD7325 is a moderate?CYP1A2?and a potent?CYP3A4?inducer in vitro^[2]. AZD7325 has the potential for the investigation of anxiety and dravet syndrome^[3]. PAM: positive allosteric modulator. In Vitro: AZD7325 is a high affinity and selective modulator of the GABAA?receptor system, exhibits high binding affinity at GABAAα1,?α2?and?α3?(K_i=0.5, 0.3, and 1.3 nM, respectively), and low at GABAAα5?(K_i=230 nM)^[4].
AZD7325 (0-10 μM; 3 consecutive days; once daily) causes a maximal CYP1A2 mRNA expression of 3.2-fold, 2.1-fold, and 2.5-fold in human hepatocytes from donor HH210, HH215, and HH216, respectively^[2].
AZD7325 (0-10 μM; 3 consecutive days; once daily) causes CYP1A2 and CYP3A4 protein expression in human hepatocytes from donor HH210^[2].
In Vivo: AZD7325 (oral administration; 10, 17.8 or 31.6 mg/kg; 30 minutes before the induction of hyperthermia) attenuates hyperthermia-induced seizures, shows median thresholds in the treatment groups of 42.8°C for 10 mg/kg, 43.3°C for 17.8 mg/kg, and 43.4°C for 31.6 mg/kg compares to 42.2°C in vehicle group^[3].