Cardiac Ca²⁺ Channel-Blocking Effects of the Cyproheptadine Derivative AH-1058 in Isolated Guinea Pig Cardiomyocytes

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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-propenyl]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.