| Autor: |
Morisawa, Tsuyoshi, Hasegawa, Junichi, Tanabe, Katsuyuki, Watanabe, Ayako, Kitano, Masayuki, Kishimoto, Yosuke |
| Zdroj: |
Journal of Pharmacy and Pharmacology; April 2000, Vol. 52 Issue: 4 p403-408, 6p |
| Abstrakt: |
The effects of trimebutine maleate, a drug commonly used to regulate motility in the gastrointestinal tract, on the delayed rectifier K+current (IK) were evaluated in guinea-pig ventricular myocytes to determine whether the drug has a proarrhythmic effect through blockade of IK.Trimebutine decreased IKin a concentration-dependent manner. To investigate the effects of trimebutine on two components of IK(IKrand IKs; rapidly activated and slowly activated components, respectively), we performed the envelope-of-tails test. Trimebutine-sensitive IKwas determined by digital subtraction of IKduring exposure to trimebutine from control IKfor each duration of the test pulse over the range 50 ms-2 s. The ratio of ΔIK, tail/ΔIKplotted against pulse duration for trimebutine-sensitive IKgradually decreased to a steady-state value as the duration of the test pulse was lengthened. This finding suggested a weak inhibitory effect of trimebutine on both IKrand IKs. The effects of trimebutine on the inward rectifier K+current (IKl) responsible for the resting potential and final repolarization phase of the action potential were investigated by applying voltage clamp ramps over a broad range of potentials. No significant effects were observed at 10 or 100 μm. We next investigated the effects of the drug on the L-type Ca2+current (ICa). Significant inhibition of ICawas observed at trimebutine concentrations greater than 10 μm.These results suggested that trimebutine maleate has weak inhibitory effects on IKr, IKsand ICaat concentrations much higher than those in clinical use. |
| Databáze: |
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