The effects of a novel Ca2+ channel blocker, KB-2796, on 5-HT-induced responses.

FUJISHIMA Yuko, HARA Hideaki, SHIMAZAWA Masamitsu, YOKOTA Koichi, SUKAMOTO Takayuki

doi:10.1254/fpj.104.19

The effects of KB-2796, a new Ca²⁺-channel blocker, on 5-hydroxytryptamine (5-HT)-induced responses were investigated in comparison with those of other Ca²⁺-channel blockers such as verapamil, flunarizine, diltiazem and nimodipine. In rat cortical membrane, KB-2796 inhibited specific [³H] spiperone binding to 5-HT₂ receptors in a competitive manner (K_i = 0.57 μM), but exhibited negligible affinity for radioligand binding to other 5-HT receptor subtypes such as 5-HT₁, 5-HT_1A, 5-HT_1B, 5-HT_1C and 5-HT₃ at a concentration of 10 or 100 μM. KB-2796 inhibited both 5-HT-stimulated shape change and 5-HT and collagen-stimulated aggregation in rabbit platelet-rich plasma with IC₅₀ values of 13.4 μM and 96.4 μM, respectively. KB-2796 also inhibited the 5-HT-induced increase of [Ca²⁺]_i, in washed rabbit platelets with the IC₅₀ value of 25.7 μM. Furthermore, KB-2796 (3-30 mg/kg, p.o.) dose-dependently inhibited the 5-HT-induced paw edema in rats. In these experiments, the inhibitory effects of KB-2796 and other Ca²⁺ channel blockers were related to their affinities for the 5-HT₂ receptor; and the potency of KB-2796 was stronger than those of diltiazem and nimodipine and almost equal to that of flunarizine, although all these inhibitors had weaker potencies than that of verapamil. These findings indicate that KB-2796 may possess antagonistic effect on the 5-HT₂ receptor.

The effects of a novel Ca2+ channel blocker, KB-2796, on 5-HT-induced responses.

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