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| Cas No.: | 942437-37-8 |
| Chemical Name: | 4-amino-8-(2-fluoro-6-methoxyphenyl)-N-propylcinnoline-3-carboxamide |
| Synonyms: | AZD7325;AZD 7325;AZD-7325 |
| SMILES: | O=C(C1=NN=C2C(C3=C(OC)C=CC=C3F)=CC=CC2=C1N)NCCC |
| Formula: | C19H19FN4O2 |
| M.Wt: | 354.385 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Publication: | [1]. Chen X, et al. The central nervous system effects of the partial GABA-Aα2,3 -selective receptor modulator AZD7325 in comparison with lorazepam in healthy males.Br J Clin Pharmacol. 2014 Dec;78(6):1298-314. [2]. Zhou D, et al. A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison.Br J Clin Pharmacol. 2012 Jul;74(1):98-108. [3]. Nomura T, et al. Potentiating α2 subunit containing perisomatic GABAA receptors protects against seizures in a mouse model of Dravet syndrome.J Physiol. 2019 Aug;597(16):4293-4307. [4]. AZD7325,Mechanism of action: Gamma-aminobutyric acid receptor A alpha 2 & 3 (GABAAα2,3) positive modulator |
| Description: | AZD7325 is a potent and orally active partial selective PAM of GABAAα2 and Aα3 receptor (Ki=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. |
| Target: | CYP1A2 CYP3A4 |
| 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. |
| 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. |
| References: | [1]. Chen X, et al. The central nervous system effects of the partial GABA-Aα2,3 -selective receptor modulator AZD7325 in comparison with lorazepam in healthy males.Br J Clin Pharmacol. 2014 Dec;78(6):1298-314. [2]. Zhou D, et al. A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison.Br J Clin Pharmacol. 2012 Jul;74(1):98-108. [3]. Nomura T, et al. Potentiating α2 subunit containing perisomatic GABAA receptors protects against seizures in a mouse model of Dravet syndrome.J Physiol. 2019 Aug;597(16):4293-4307. [4]. AZD7325,Mechanism of action: Gamma-aminobutyric acid receptor A alpha 2 & 3 (GABAAα2,3) positive modulator |