Effect of 5-{3-[((2S)-l,4-Benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCl (MKC-242), a Novel 5-HT1A-Receptor Agonist, on Aggressive Behavior and Marble Burying Behavior in Mice

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  • Abe Michikazu
    Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation
  • Nakai Hiroshi
    Pharmacokinetics and Metabolism Research Laboratory, Yokohama Research Center, Mitsubishi Chemical Corporation
  • Tabata Reiko
    Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation
  • Saito Ken-Ichi
    Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation
  • Egawa Mitsuo
    Clinical Research Department, Mitsubishi Chemical Corporation

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タイトル別名
  • Effect of 5-{3-(((2S)-1,4-Benzodioxan-2-ylmethyl)amino)propoxy}-1,3-benzodioxole HCl (MKC-242), a Novel 5-HT1A-Receptor Agonist, on Aggressive Behavior and Marble Burying Behavior in Mice.
  • Effect of 5 3 2S 1 4 Benzodioxan 2 ylme
  • Effect of 5-{3-[((25)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HCl (MKC-242), a novel 5-HT!A-receptor agonist, on aggressive behavior and marble burying behavior in mice

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Behavioral effects of 5-｛3-[((2S)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy｝-1, 3-benzodioxole HCl (MKC-242), a novel 5-HT1A-receptor agonist, were evaluated using animal models of anxiety and obsessive compulsive disorder and compared against reference compounds. MKC-242 suppressed foot shock-induced fighting behavior without loss of motor coordination in mice as the reference compounds did. The ED50 values of MKC-242, buspirone, tandospirone and diazepam were 1.7, 42, 80 and 2.0 mg/kg, p.o., respectively. The duration of the suppression of fighting by MKC-242 was longer than those of buspirone and tandospirone and comparable to that of diazepam. Similar results were also obtained with the water-lick conflict test in rats. The plasma concentration of MKC-242 in rats was much higher than the reported value of buspirone during 0.25 – 6 hr after oral administration. In addition, MKC-242 reduced marble burying behavior without reduction of motor activity. Fluoxetine, tandospirone and diazepam also reduced the behavior at non-sedative doses. These findings indicate that MKC-242 possesses a longer-lasting anxiolytic effect than azapirones. This might be due to the high concentration of the compound in plasma. In addition, it is also suggested that MKC-242 possesses an antiobsessional effect.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 76 (3), 297-304, 1998

    公益社団法人 日本薬理学会

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