In Vitro Pharmacological Characteristics of SKP-450, A Novel K+ Channel Opener, in
Non-Vascular Smooth Muscles in Comparison with Levcromakalim. Ki Whan HongI, Ji Young
Park\ Hyun Hee Kim\ and Sung-Eun Y002 lDepartment of Pharmacology, College of Medicine, Pusan National
University, Pusan, 602-739; and 2Korea Research Institute of Chemical Technology, Daejeon, Korea
In the present study, we characterized the non-vascu1ar smooth musc1e relaxant effects of a novel benzoyran
derivative, SKP-450 (2- [2" (1" ,3" -dioxolone)-2-methyl-4-(2’ -oxo-l ’ -pyrrolidinyl)-6-띠tro-2H-l- benzopyran) and its
metabolite, SKP-31O, in comparison with levcromakalim (LCRK). In the rat stomach fundus, the spontaneous
6.5
motility stimulated by 10 -V., M bethanechol was complete1y e1iminated not on1y by 10 -, M SKP-450 but also
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by 10 V M LCRK, which were blocked by 10 V M glibenc1amide. The inhibitory effect of SKP-450 (pD2, 3.94:t
0.66) was much less than LCRK (pD2, 5.73:t0.38, P<0.05). In the bethanechol (10 6.5 M)-stimulated utinary
bladder, the tonus was decreased in association with elimination of spontaneous motility by 10 7 M SKP-450
and 10-
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M LCRK (pD2, 6.77:t0.06) (P<0.05), which were inhibitable by 10-M glibenc1amide. The inhibitory
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effect of SKP-450 (pD2, 7.66:t0.05) was significant1y more potent than that of LCRK (pD2, 6.77 :t0.06, P< 0.05).
In the rat uterus stimulated by PGF2α (10-
7
M), both increased tonus and spontaneous motility were e1iminated
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by 10 V M LCRK with slight depression of the tonus, but not by SKP-450 (10 J M). The stimulated trachea
of guinea-pig by 10 6 V.J M bethanechol was moderately suppressed by SKP-450 (10 V