| Description | AZD1283 is an effective P2Y12 receptor antagonist (EC50: 3.0 ug/kg/min, binding IC50: 11 nM). AZD1283 dose-dependently induced increases in blood flow and inhibition of ADP-induced platelet aggregation with antithrombotic ED50 values of 3.0 and 10 μg/kg/min, respectively. The doses induced the increase in bleeding time at 33 and 100 μg/kg/min for 3- and 13-fold, respectively. Thus, the therapeutic index (TI) was ≥10 for both compounds. |
| In vivo | 急性给药dasotraline剂量依赖性降低LC NE、VTA DA和DR 5-HT神经元的自发性发火率，分别通过激活α2、D2和5-HT1A自受体实现。Dasotraline主要抑制LC NE神经元的发火率，而对VTA DA和DR 5-HT神经元放电仅产生部分降低。SEP-225289在抑制5-HT和NE传输器方面具有同等效力，因为它同样延长了由微电泳应用的5-HT和NE诱导的背侧海马CA3锥体神经元发火活动的50%恢复时间所需的时间【1】。SEP-225289的逐步增加剂量会增加平均多巴胺和血清素转运体的占据率。对于8 mg，平均多巴胺和血清素转运体占据率分别为33%±11%和2%±13%；对于12 mg，分别为44%±4%和9%±10%；对于16 mg，分别为49%±7%和14%±15%【2】。 |
| Target activity | P2Y12 receptor:11 nM |
| molecular weight | 470.54 |
| Molecular formula | C23H26N4O5S |
| CAS | 919351-41-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 22.5 mg/mL (47.82 mM) |
| References | 1. Bach P,et al. Lead optimization of ethyl 6-aminonicotinate acyl sulfonamides as antagonists of the P2Y12 receptor. separation of the antithrombotic effect and bleeding for candidate drug AZD1283. J Med Chem. 2013 Sep 12;56(17):7015-24. |