비-혈관평활근에서 새로운 K+ 동로 개방제인 SKP-450의약리 학적 작용의 특성 -Levcromakalim의 작용과 비 교

In Vitro Pharmacological Characteristics of SKP-450， A Novel K + Channel Opener， in Non-Vascular Smooth Muscles in Comparison with Levcromakalim.

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 itsmetabolite， 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 6 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 10-6M LCRK (pD2， 6.77:t0.06) (P<0.05)， which were inhibitable by 10-M glibenc1amide. The inhibitory 6effect 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 (10-7M)， both increased tonus and spontaneous motility were e1iminated 5 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 &#1048637; 10 J M) but litt1e by SKP-31O. In association with the relaxant effects， SKP-450 (10 6 M) and LCRK (10 5 M) caused a significant stimulation of the 86Rb eff1ux from rat urinary bladder and stomach fundus， which were antagonized by 10 - 5M glibenc1amide， whereas the K channel openers could not exert a stimulation of the 86Rb eff1ux from rat + uterus. In conc1usion， it is suggested that SKP-450 exerts potent r‘e1axant effects on the urinaηr bladder detrusor musc1e and duodenum， whereas it shows much less effect on stomach fundus and uterus as contrasted to LCRK.