Involvement of Potassium Channels in Spinal Antinociceptions Induced by Fentanyl, Clonidine and Bethanechol in Rats.

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  • Yamazumi Isao
    Department of Anesthesiology, Kinki University School of Medicine
  • Okuda Takahiko
    Department of Anesthesiology, Kinki University School of Medicine
  • Koga Yoshihisa
    Department of Anesthesiology, Kinki University School of Medicine

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In the central nervous systems, intracellular and extracellular movement of potassium ions plays an important role in regulating neuronal excitability and the release of neurotransmitters. The purpose of our study was to determine whether nicorandil (adenosine triphosphate-sensitive K+ channel opener) exerts antinociceptive effects by itself or in combination with fentanyl, clonidine and bethanechol and whether glibenclamide (adenosine triphosphate-sensitive K+ channel blocker) and charybdotoxin (Ca2+-activated K+ channel blocker) may antagonize the antinociceptive action of fentanyl, clonidine and bethanechol. Antinociceptive effects were assessed using the tail-flick test in rats. Nicorandil (100 μg) and antinociceptively ineffective doses of fentanyl (1 μg), clonidine (2.5 μg) or bethanechol (10 μg) were coadministered intrathecally (i.t.). Glibenclamide (100 μg) or charybdotoxin (2.5 ng) were administered i.t. at 5 min before each effective dose of fentanyl (2.5 μg), clonidine (10 μg) or bethanechol (40 μg). The present findings demonstrated that i.t. administration of nicorandil alone exerted no influence on the tail-flick latency. However, concomitant administrations of antinociceptively inactive doses of fentanyl, clonidine or bethanechol with nicorandil elicited significant suppression of the thermonociceptive response. Also, each antinociception induced by fentanyl, clonidine or bethanechol was partially antagonized by both glibenclamide and charybdotoxin. These findings showed that activation of the K+ channel might enhance the antinociceptive effects of fentanyl, clonidine and bethanechol.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 87 (4), 268-276, 2001

    公益社団法人 日本薬理学会

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