Yamamoto Takashi, Niwa Seiji, Iwayama Satoshi, Koganei Hajime, Fujita Shin-ichi, Takeda Tomoko, Kito Morikazu, Ono Yukitsugu, Saitou Yuki, Takahara Akira, Iwata Seinosuke, Yamamoto Hiroshi, Shoji Masataka
Pharmaceutical Research Laboratory, Ajinomoto company Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Japan.
Bioorg Med Chem. 2006 Aug 1;14(15):5333-9. doi: 10.1016/j.bmc.2006.03.040. Epub 2006 Apr 17.
Antiallergic drug cyproheptadine (Cyp) is known to have inhibitory activities for L-type calcium channels in addition to histamine and serotonin receptors. Since we found that Cyp had an inhibitory activity against N-type calcium channel, Cyp was optimized to obtain more selective N-type calcium channel blocker with analgesic action. As a consequence of the optimization, we found 13 with potent N-type calcium channel inhibitory activity which had lower inhibitory activities against L-type calcium channel, histamine (H1), and serotonin (5-HT2A) receptors than those of Cyp. 13 showed an oral analgesic activity in rat formalin-induced pain model.
抗过敏药物赛庚啶（Cyp）除了作用于组胺和5-羟色胺受体外，还已知对L型钙通道具有抑制活性。由于我们发现Cyp对N型钙通道具有抑制活性，因此对Cyp进行优化以获得更具选择性且具有镇痛作用的N型钙通道阻滞剂。优化的结果是，我们发现了13种具有强效N型钙通道抑制活性的物质，它们对L型钙通道、组胺（H1）和5-羟色胺（5-HT2A）受体的抑制活性低于Cyp。13在大鼠福尔马林诱导的疼痛模型中显示出口服镇痛活性。
