Interaction of orally administered 5-[3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole (MKC-242) with 5-HT1A receptors in rat brain

Jpn J Pharmacol. 1997 May;74(1):69-75. doi: 10.1254/jjp.74.69.

Abstract

The present study was carried out to clarify whether orally administered 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-be nzodioxole (MKC-242), a serotonin1A (5-HT1A)-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 3[H]8-hydroxy-2-(di-n-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 [3H]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-HT1A 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.

Publication types

  • Comparative Study

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacokinetics
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Autoradiography
  • Binding, Competitive / drug effects
  • Brain / anatomy & histology
  • Brain / drug effects
  • Brain Chemistry / drug effects*
  • Dioxanes / pharmacokinetics
  • Dioxanes / pharmacology*
  • Dioxoles / pharmacokinetics
  • Dioxoles / pharmacology*
  • Male
  • Neurons / drug effects
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Serotonin / physiology
  • Serotonin Agents / pharmacology
  • Serotonin Receptor Agonists / pharmacokinetics
  • Serotonin Receptor Agonists / pharmacology*

Substances

  • Dioxanes
  • Dioxoles
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin Receptor Agonists
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • osemozotan