title: Structure-activity relationship study of 1,4-dihydropyridine derivatives blocking N-type calcium channels.
abstract: Cilnidipine is a 1,4-dihydropyridine derived L/N-type calcium channel dual blocker possessing neuroprotective and analgesic effects which are related to its N-type calcium channel inhibitory activity. In order to find specific N-type calcium channel blockers with the least effects on cardiovascular system, we performed structure-activity relationship study on APJ2708, which is a derivative of cilnidipine, and found a promising N-type calcium channel blocker 21b possessing analgesic effect in vivo with a 1600-fold lower activity against L-type calcium channels than that of cilnidipine.
authors.affiliation: Pharmaceutical Research Laboratory, Ajinomoto company Inc., 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: Seiji
authors.initials: S
authors.lastname: Ohno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Onishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsueda
authors.forename: Hajime
authors.initials: H
authors.lastname: Koganei
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Uneyama
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: Masataka
authors.initials: M
authors.lastname: Shoji
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects*; D004095:Dihydropyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005557:Formaldehyde / Q000737:chemistry; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D004095:Dihydropyridines; D005557:Formaldehyde; C038806:1,4-dihydropyridine; C065927:cilnidipine