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

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Abstract

Behavioral effects of 5-{3-[((2<I>S</I>)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy}-1, 3-benzodioxole HCl (MKC-242), a novel 5-HT<SUB>1A</SUB>-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 ED<SUB>50</SUB> 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.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 76(3), 297-304, 1998-03

    The Japanese Pharmacological Society

References:  31

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008192063
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4440449
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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