A 582941

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

A 582941 是 α7 nAChR 的选择性激动剂，A-582941 被发现对 α7 nAChR 表现出高亲和力结合和部分激动作用。体外和体内研究表明，A-582941 可激活已知参与认知功能的信号通路，例如 ERK1/2 和 CREB 磷酸化。

A 582941 is a Selective agonist of α7 nAChR partialA-582941 was found to exhibit high-affinity binding and partial agonism at alpha7 nAChRs.?In vitro and in vivo studies indicated that A-582941 activates signaling pathways known to be involved in cognitive function such as ERK1/2 and CREB phosphorylation.?A-582941 enhanced cognitive performance in behavioral models that capture domains of working memory, short-term recognition memory, memory consolidation, and sensory gating deficit.?A-582941 exhibited a benign secondary pharmacodynamic and tolerability profile as assessed in a battery of assays of cardiovascular, gastrointestinal, and CNS function.

A-582941 (0.1-100 μM) protects against cell death induced by NGF withdrawal in PC12 cells.A-582941 (100 nM) increases the number of inhibitory postsynaptic potentials (IPSCs) by 260±70%, the sum of amplitudes by 220±30%, and the sum of areas by 210±40%.A-582941 increases ERK1/2 phosphorylation with an EC50 of 95 nM in PC12 cells.

A-582941 (3 μM/kg, i.p. once daily for 3 d) induces a moderate increase in ACh release in the medial prefrontal cortex (mPFCx) of freely moving rats.A-582941 (0.01-1.00 μM/kg, i.p.) produces a dose-dependent increase in ERK1/2 phosphorylation in the cingulate cortex and hippocampus, and increases cAMP response element-binding protein (CREB) phosphorylation in the cingulate cortex in mice.A-582941 (0.1-1.0 μM/kg, i.p.) evokes dose-dependent increases in Ser-9 GSK-3β phosphorylation in the mouse cingulate cortex.A-582941 shows high oral bioavailability (mouse ~100%, rat 90%, dog 22%, monkey 50%) and Cmax (mouse 18, rat 114, dog 79, monkey 39 ng/mL) following oral administration (mouse 1.0, rat 6.2, dog 3.0, monkey 3.0 μM/kg).A-582941 shows terminal elimination half-lives (mouse 1.4, rat 1.5, dog 1.4, monkey 2.0 h), plasma clearance (mouse 7.9, rat 4.7, dog 5.3, monkey 1.6 L/h/kg) and volumes of distribution (mouse 11.4, rat 9.2, dog 7.9, monkey 3.9 L/kg) following intravenous administration (mouse 1.0, rat 6.2, dog 0.5, monkey 0.5 μM/kg). Animal Model:Male Sprague-Dawley CD rats (250-275 g)Dosage:3 μM/kg Administration:I.p. once daily for 3 days Result:Increased the releases of Ach.The effect remained stable after the second and third administration.

——

Endocrinology/Hormones

AChR

α7 nAChR

——

——

848591-90-2

280.37

C17H20N4?

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (283.05 mM)

[H][C@@]12CN(C)C[C@]1([H])CN(C2)c1ccc(nn1)-c1ccccc1

——

(-20℃)

With Ice Pack

≥ 2 years