Antalarmin hydrochloride, a pyrrolopyrimidine, is a potent, small molecule, nonpeptide CRF1 (Corticotropin-Releasing Factor Receptor 1) selective receptor antagonist. Antalarmin hydrochloride exhibits high affinity for the CRF1 (Ki=2.7nM), but not CRF2 receptor as determined in Lt-K-mouse fibroblast cells[1].
In vitro, Antalarmin hydrochloride (100nM) treatment for 48 hours blocked CRF-induced increases in PKAIIβ levels in primary hippocampal neurons derived from Tg2576 mice[2].
In vivo, intraperitoneal administration of Antalarmin hydrochloride at doses of 5, 10, and 20mg/kg for 7 days produced dose-dependent decreases in Aβ1-42 levels in Tg2576 mice[2]. Furthermore, treatment with Antalarmin hydrochloride at 20mg/kg for 6 months significantly reduced Aβ1-42 levels and Aβ plaque deposition in the cortex of Tg2576 mice[2]. In BALB/cByJIco male mice, intraperitoneal administration of Antalarmin hydrochloride at 10mg/kg daily for 4 weeks significantly improved the physical state of the mice and induced a nonsignificant decrease in time spent in the lit box (TLB) and activity[3].
References:
[1] Zorrilla EP, Schulteis G, Ormsby A, et al. Urocortin shares the memory modulating effects of corticotropin-releasing factor (CRF): mediation by CRF1 receptors. Brain Res. 2002;952(2):200-210.
[2] Dong H, Wang S, Zeng Z, et al. Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-β and behavior in Tg2576 mice. Psychopharmacology (Berl). 2014;231(24):4711-4722.
[3] Ducottet C, et al. Effects of the selective nonpeptide corticotropin-releasing factor receptor 1 antagonist Antalarmin hydrochloride in the chronic mild stress model of depression in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):625-31.
Antalarmin hydrochloride，一种吡咯嘧啶，是一种有效的小分子非肽CRF1（促肾上腺皮质激素释放因子受体1）的选择性受体拮抗剂。在Lt-K小鼠成纤维细胞中，Antalarmin hydrochloride对CRF1具有高亲和力（Ki=2.7nM），但对CRF2受体没有亲和力[1]。
体外实验中，Antalarmin hydrochloride（100nM）处理48小时可阻断CRF诱导的Tg2576小鼠海马原代神经元PKAIIβ水平升高[2]。
体内实验中，在Tg2576小鼠中，腹腔注射Antalarmin hydrochloride（5、10 和 20mg/kg）连续给药7天，可剂量依赖性地降低Aβ1-42水平。此外，以20mg/kg剂量给予Antalarmin hydrochloride持续6个月，可显著降低Tg2576小鼠皮层中的Aβ1-42水平及Aβ斑块沉积[2]。在BALB/cByJIco雄性小鼠中，每天以10mg/kg的剂量腹腔注射Antalarmin hydrochloride，连续4周显著改善了小鼠的身体状态，且不影响小鼠在点亮盒（TLB）中的时间和活动[3]。