Novel Benzodioxan Derivative, 5-{3-[((2S)-1,4-Benzodioxan-2-ylmethyl)amino]propoxy}-l,3-benzodioxole HC1 (MKC-242), with a Highly Potent and Selective Agonist Activity at Rat Central Serotonin1A Receptors

• Matsuda Toshio

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Yoshikawa Takashi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Suzuki Makoto

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Asano Shoichi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Somboonthum Pranee

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Takuma Kazuhiro

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Nakano Yoshihide

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Morita Tomoko

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Nakasu Yukiko

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Kim Hye Sun

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

• Egawa Mitsuo

  Research and Development Department, Mitsubishi Chemical Co.

• Tobe Akihiro

  Research and Development Department, Mitsubishi Chemical Co.

• Baba Akemichi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University

書誌事項

タイトル別名

• Novel Benzodioxan Derivative, 5-{3-(((2S)-1,4-Benzodioxan-2-ylmethyl)amino)propoxy}-1,3-benzodioxole HCl (MKC-242), with a Highly Potent and Selective Agonist Activity at Rat Central Serotonin1A Receptors.
• Novel benzodioxan derivative, 5-{3-[((2S)-l,4-benzodioxan-2-ylmethyl)amino]propoxy}-l,3-benzodioxole HC1 (MKC-242), with a highly potent and selective agonist activity at rat serotonin1A receptors
• Novel benzodioxanderivative, 5-(3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy)-1,3-benzodioxole HCl (MKC-242), with a highly potent and selective agonist activity at rat central serotoniniA receptors
• Novel benzodioxan derivative, 5-{3-[((2S)-1,4-benzodioxan-2-ylmethyl)amino]propoxy}-1,3-benzodioxole HC1 (MKC-242), with a highly potent and selective agonist activity at rat serotonin 1A receptors

抄録

The present study characterizes the neurochemical profile of the newly synthesized compound 5-{3-[((2S)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy}-1, 3-benzodioxole HC1 (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin_1A (5-HT_1A) receptors (K₁: 0.35 nM) and moderate affinity for α₁-adrenoceptors (K_i: 21 nM), whereas it had no appreciable affinity for any other neurotrans-mitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT_1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT_1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT_1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT_1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropanamide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT_1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT_1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT_1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT_1A receptors, respectively, in the central nervous system.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 69 (4), 357-366, 1995

  公益社団法人 日本薬理学会

キーワード

• Serotonin (5-HT)
• 5-HT<SUB>1A</SUB> receptor
• MKC-242
• Agonist

詳細情報

• CRID: 1390001204287384960
• NII論文ID: 10006063729
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.69.357
• COI: 1:CAS:528:DyaK28XlslWi
• ISSN: 13473506
• ISSN: 00215198
• ISSN: http://id.crossref.org/issn/00215198
• PubMed: 8786639
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819353958?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819353958?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/1996132141
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可