title: Discovery, structure-activity relationship study, and oral analgesic efficacy of cyproheptadine derivatives possessing N-type calcium channel inhibitory activity.
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.
authors.affiliation: Pharmaceutical Research Laboratory, Ajinomoto company Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Niwa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Iwayama
authors.forename: Hajime
authors.initials: H
authors.lastname: Koganei
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Fujita
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takeda
authors.forename: Morikazu
authors.initials: M
authors.lastname: Kito
authors.forename: Yukitsugu
authors.initials: Y
authors.lastname: Ono
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saitou
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Seinosuke
authors.initials: S
authors.lastname: Iwata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masataka
authors.initials: M
authors.lastname: Shoji
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D045744:Cell Line, Tumor; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005557:Formaldehyde / Q000737:chemistry; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011968:Receptors, Histamine / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D011968:Receptors, Histamine; D011985:Receptors, Serotonin; D005557:Formaldehyde; D003533:Cyproheptadine