Cardiac Ca2+ channel-blocking effects of the cyproheptadine derivative AH-1058 in isolated guinea pig cardiomyocytes

Abstract

The Ca2+ 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-p ropenyl]piperidine hydrochloride) was quantitatively assessed using isolated guinea pig cardiomyocytes. AH-1058 (0.001 - 10 μM) and its mother compound cyproheptadine (1 - 100 μM) reduced the Ca2+ currents elicited from the holding potential of -80 or -40 mV. The IC50 values for cyproheptadine at holding potentials of -80 and -40 mV were 42.44 and 7.75 μM, respectively, whereas those for AH-1058 were 4.91 and 0.32 μM, respectively, whose potency was equivalent to those of the typical Ca2+ channel blocker verapamil. These results suggest that the introduction of the cinnamil structure to cyproheptadine can generate a potent L-type Ca2+ channel-blocking compound as potent as verapamil.