Cardiac Ca(2+) channel-blocking effects of the cyproheptadine derivative AH-1058 in isolated guinea pig cardiomyocytes

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 mo...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmacological sciences 2003-02, Vol.91 (2), p.163-166
Main Authors: Dohmoto, Hideki, Takahara, Akira, Uneyama, Hisayuki, Yoshimoto, Ryota
Format: Article
Language:English
Subjects:
Animals
Bridged Bicyclo Compounds - pharmacology
Calcium Channel Blockers - pharmacology
Calcium Channels, L-Type - drug effects
Cell Separation
Cyproheptadine - analogs & derivatives
Cyproheptadine - pharmacology
Dose-Response Relationship, Drug
Electrophysiology
Guinea Pigs
Heart - drug effects
In Vitro Techniques
Male
Myocardium - cytology
Patch-Clamp Techniques
Piperidines - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1347-8613
DOI:10.1254/jphs.91.163