AZD-7325

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

AZD-7325 是一种有效的 α2/3 功能选择性部分 GABAA 受体调节剂，pKi 为 9.51。

AZD-7325 is a potent, α2/3 functionally selective, partial GABAA receptor modulator with pKi of 9.51; exerts neutral antagonism at the α1-subunit and partial efficacy at the α2,3-subunits over the α5-subunit; AZD7325 is expected to reduce the risk for the benzodiazepine like side effects, such as sedation and cognitive effects, and shows potential for the treatment of anxiety.Anxiety Phase 1 Clinical(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).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.AZD7325 (0-10 μM; 3 consecutive days; once daily) causes CYP1A2 and CYP3A4 protein expression in human hepatocytes from donor HH210.(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.

RT-PCRCell Line:Primary human hepatocytes from one female (HH210) and two male (HH215, HH216) donorsConcentration:0.01, 0.1, 1, 10 μM Incubation Time:3 consecutive days Result:Led to increase of CYP1A2 mRNA expression.Western Blot Analysis 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.

Animal Model:Male and female P18 - P20 F1.Scn1a+/- mice 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.

AZD7325

Membrane Transporter/Ion Channel

GAT

GAT

Neurological Disease

Anxiety

942437-37-8

354.385

C19H19FN4O2

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (282.18 mM)

O=C(C1=NN=C2C(C3=C(OC)C=CC=C3F)=CC=CC2=C1N)NCCC

4-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylcinnoline-3-carboxamide

(-20℃)

With Ice Pack

≥ 2 years