Discovery, structure-activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity

  • Bioorg Med Chem. 2006 Aug 1;14(15):5333-9. doi: 10.1016/j.bmc.2006.03.040.
Takashi Yamamoto  1 ,  Seiji Niwa ,  Satoshi Iwayama ,  Hajime Koganei ,  Shin-ichi Fujita ,  Tomoko Takeda ,  Morikazu Kito ,  Yukitsugu Ono ,  Yuki Saitou ,  Akira Takahara ,  Seinosuke Iwata ,  Hiroshi Yamamoto ,  Masataka Shoji
Affiliations
  • 1. Pharmaceutical Research Laboratory, Ajinomoto company Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Japan.
PMID: 16616501 DOI: 10.1016/j.bmc.2006.03.040
Abstract

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.

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