Archives of Pharmacal Research

, Volume 32, Issue 3, pp 413–420

Inhibition of intestinal motility by the putative BKCa channel opener LDD175

Authors

  • Ike Campomayor dela Peña
    • College of PharmacySahmyook University
  • Seo Young Yoon
    • College of PharmacySahmyook University
  • Sung Mok Kim
    • College of PharmacySahmyook University
  • Geum Seon Lee
    • College of PharmacySahmyook University
  • Chul-Seung Park
    • College of PharmacySahmyook University
    • Department of Life ScienceGwangju Institute of Science and Technology
  • Yong Chul Kim
    • Department of Life ScienceGwangju Institute of Science and Technology
    • College of PharmacySahmyook University
Research Articles Drug Actions

DOI: 10.1007/s12272-009-1315-x

Cite this article as:
dela Peña, I.C., Yoon, S.Y., Kim, S.M. et al. Arch. Pharm. Res. (2009) 32: 413. doi:10.1007/s12272-009-1315-x

Abstract

LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated (BKCa) channels. Activators of the BKCa channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner (pEC50=5.9 ± 0.1) (Emax=96 ± 1.0% at 100 μM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC50=5.3 ± 0.1)(Emax=97.7 ± 2.3%, n=6) and electrical field stimulation (EFS) (pEC50=5.5 ± 0.1) (Emax=83.3 ± 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC50 of 6.1 ± 0.1 and Emax of 96.6 ± 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC50 and Emax values of 4.1 ± 0.1 and 50.8 ± 5.0% (n=3). BKCa channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl2), and glibenclamide (KIR and KATP channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BKCa channels.

Key words

LDD175BenzofuroindoleBKCa ChannelsIleumAntispasmodicIbTX
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© The Pharmaceutical Society of Korea 2009