Research Articles Drug Actions

Archives of Pharmacal Research

, Volume 32, Issue 3, pp 413-420

First online:

Inhibition of intestinal motility by the putative BKCa channel opener LDD175

  • Ike Campomayor dela PeñaAffiliated withCollege of Pharmacy, Sahmyook University
  • , Seo Young YoonAffiliated withCollege of Pharmacy, Sahmyook University
  • , Sung Mok KimAffiliated withCollege of Pharmacy, Sahmyook University
  • , Geum Seon LeeAffiliated withCollege of Pharmacy, Sahmyook University
  • , Chul-Seung ParkAffiliated withCollege of Pharmacy, Sahmyook UniversityDepartment of Life Science, Gwangju Institute of Science and Technology
  • , Yong Chul KimAffiliated withDepartment of Life Science, Gwangju Institute of Science and Technology
  • , Jae Hoon CheongAffiliated withCollege of Pharmacy, Sahmyook University Email author 

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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) (E max=96 ± 1.0% at 100 μM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC50=5.3 ± 0.1)(E max=97.7 ± 2.3%, n=6) and electrical field stimulation (EFS) (pEC50=5.5 ± 0.1) (E max=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 E max of 96.6 ± 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC50 and E max 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

LDD175 Benzofuroindole BKCa Channels Ileum Antispasmodic IbTX