| In Vitro |
AZD7325 is a high affinity and selective modulator of the GABAA receptor system, exhibits high binding affinity at GABAAα1, α2 and α3 (Ki=0.5, 0.3, and 1.3 nM, respectively), and low at GABAAα5 (Ki=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]. RT-PCR[2] Cell Line: Primary human hepatocytes from one female (HH210) and two male (HH215, HH216) donors Concentration: 0.01, 0.1, 1, 10 µM Incubation Time: 3 consecutive days Result: Led to increase of CYP1A2 mRNA expression Western Blot Analysis[2] Cell Line: Primary human hepatocytes from donors Concentration: 0.01, 0.1, 1, 10 µM Incubation Time: 3 consecutive days Result: Increased CYP1A2 and CYP3A4 protein level.
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| 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]. Animal Model: Male and female P18 - P20 F1.Scn1a+/- mice[3] Dosage: 10, 17.8 or 31.6 mg/kg Administration: Oral administration; 30 minutes before the induction of hyperthermia Result: Attenuated hyperthermia-induced seizures in F1.Scn1a+/- mice with no sedative effect.
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