title: Cardiac Ca(2+) channel-blocking effects of the cyproheptadine derivative AH-1058 in isolated guinea pig cardiomyocytes.
abstract: The Ca(2+) channel-blocking efficacy of the cyproheptadine derivative AH-1058 (4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-propenyl]piperidine hydrochloride) was quantitatively assessed using isolated guinea pig cardiomyocytes. AH-1058 (0.001 - 10 microM) and its mother compound cyproheptadine (1 - 100 microM) reduced the Ca(2+) currents elicited from the holding potential of -80 or -40 mV. The IC(50) values for cyproheptadine at holding potentials of -80 and -40 mV were 42.44 and 7.75 microM, respectively, whereas those for AH-1058 were 4.91 and 0.32 microM, respectively, whose potency was equivalent to those of the typical Ca(2+) channel blocker verapamil. These results suggest that the introduction of the cinnamil structure to cyproheptadine can generate a potent L-type Ca(2+) channel-blocking compound as potent as verapamil.
authors.affiliation: Pharmaceutical Research Laboratories, Pharmaceuticals Company, Ajinomoto Co, Inc, Kawasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Dohmoto
authors.forename: Akira
authors.initials: A
authors.lastname: Takahara
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Uneyama
authors.forename: Ryota
authors.initials: R
authors.lastname: Yoshimoto
mesh_terms: D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects; D002469:Cell Separation; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*
chemical_list: D001643:Bridged Bicyclo Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010880:Piperidines; D003533:Cyproheptadine; C119283:AH 1058