SIB 1757

mGluR5a拮抗剂；选择性抑制表达人类mGluR5a的成纤维细胞中谷氨酸诱导的钙释放和quisqualate诱导的磷酸肌醇积累（IC50s分别为0.37和3.1µM），而抑制表达mGluR1b的成纤维细胞（两者的IC50s=>100µM）；对mGluR5a具有选择性，优于mGluR2、mGluR3、mGluR4a、mGluR6、mGluR7b、mGluR8（所有IC50s=>100µM）以及AMPA、kainate和NMDA受体（所有IC50s=>30µM）；抑制新生大鼠分离的海马和纹状体中(S)-3,5-DHPG诱导的磷酸肌醇积累（IC50s分别为5.2和10.1µM）；鞘内给药以0.01µg/只的剂量增加脊髓神经结扎诱发的神经性疼痛大鼠模型中的爪子缩回阈值。An antagonist of mGluR5a; selectively inhibits glutamate-induced calcium release and quisqualate-induced phosphoinositol accumulation in fibroblasts expressing human mGluR5a (IC50s = 0.37 and 3.1 µM, respectively) over mGluR1b-expressing fibroblasts (IC50s = >100 µM for both); selective for mGluR5a over mGluR2, mGluR3, mGluR4a, mGluR6, mGluR7b, mGluR8 (IC50s = >100 µM for all) as well as AMPA, kainate, and NMDA receptors (IC50s = >30 µM for all); inhibits (S)-3,5-DHPG-induced phosphoinositol accumulation in isolated neonatal rat hippocampus and striatum (IC50s = 5.2 and 10.1 µM, respectively); intrathecal administration increases the paw withdrawal threshold in a rat model of spinal nerve ligation-induced neuropathic pain at 0.01 µg/animal.分子式C12H11N3O分子量213.2OC1=C(/N=N/C2=CC=CC=C2)N=C(C)C=C1