Interaction of Orally Administered 5-{3-[((2S)-1,4-Benzodioxan-2-ylmethyl)amino]propoxy} - 1,3-benzodioxole (MKC-242)with 5-HT_<1A> Receptors in Rat Brain

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Author(s)

Abstract

The present study was carried out to clarify whether orally administered 5-{3-[((2<I>S</I>)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy}-1, 3-benzodioxole (MKC-242), a serotonin<SUB>1A</SUB> (5-HT<SUB>1A</SUB>)-receptor agonist having potent anxiolytic-like and antidepressant-like effects in animal models, binds to 5-HT1A receptors in rat brain. Quantitative autoradiography showed that orally administered MKC-242 (0.1-0.5 mg/kg)caused a significant decrease in [<SUP>3</SUP>H]8-hydroxy-2-(di-<I>n</I>-propylamino)tetralin (8-OH-DPAT)binding in the hippocampus and dorsal raphe nucleus sections. The decrease in the binding by MKC-242 was observed up to 4 hr after administration, and the effective doses were similar to those in its anxiolytic-like effect in the animal models. Repeated treatment of MKC-242 (0.5 mg/kg/day, p.o.)or buspirone (30 mg/kg/day, p.o.)for 2 weeks did not affect [<SUP>3</SUP>H]8-OH-DPAT binding in both sections. These results suggest that orally administered MKC-242 at the low doses that do not show 5-HT1A-receptor-mediated in vivo responses such as the hypothermic effect, adrenocortical effect and the decrease in 5-HT turnover passes the blood-brain barrier and subsequently binds to 5-HT<SUB>1A</SUB> receptors in rat brain. In addition, they indicate that repeated stimulation of the receptors by the agonists does not affect the number of the binding sites.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 74(1), 69-75, 1997-05-01

    The Japanese Pharmacological Society

References:  29

Codes

  • NII Article ID (NAID)
    10008678452
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4219984
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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