Activation of Cerebral Function by CS-932, a Functionally Selective M1Partial Agonist. Neurochemical Characterization and Pharmacological Studies.

DOI Web Site Web Site Web Site Web Site ほか1件をすべて表示 一部だけ表示 被引用文献2件 参考文献78件
  • Iwata Nobuyoshi
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Kozuka Masao
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Hara Takao
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Kaneko Tsugio
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Tonohiro Toshiyuki
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Sugimoto Masahiko
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Niitsu Yoichi
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Kondo Yusuke
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Yamamoto Tsuneyuki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 1-1, Maidashi 3-chome, Higashi-ku, Fukuoka 812-8582, Japan
  • Sakai Jun-ichi
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan
  • Nagano Mitsuo
    Neurosience and Immunology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan

この論文をさがす

抄録

A newly synthesized agonist for muscarinic acetylcholine (ACh) receptors CS-932, (R)-3-(3-isoxazoloxy)-1-azabicyclo-[2.2.2] octane hydrochloride, showed a relatively higher affinity for M1 than M2 receptors expressed in Chinese hamster ovary (CHO)-cells in comparison with ACh. CS-932 elevated the intracellular Ca2+ level only in M1-CHO cells, although ACh increased the level in both M1- and M3-CHO cells. CS-932 and ACh reduced forskolin-stimulated accumulation of cAMP in M2-CHO cells by 20% and 80%, respectively. This neurochemical profile of CS-932 indicates that the compound can activate M1-receptor-mediated functions selectively. CS-932 increased firing of cholinoceptive neurons in rat hippocampal slices, and this excitation was antagonized by pirenzepine, but not by AF-DX116. CS-932 increased awake and decreased slow wave sleep episodes of daytime EEG in free-moving rats. It counteracted scopolamine-induced slow waves in rat cortical EEG. CS-932 also increased the power of α- and β-waves, but decreased δ-wave of the cortical EEG in anesthetized monkeys. It ameliorated scopolamine-induced impairment of working memory in rats. Orally administered CS-932 had the best penetration into the brain among the muscarinic agonists tested and caused the least salivary secretion among the cholinomimetics examined. These results indicate that CS-932 has potential as a cognitive enhancer with fewer side effects in therapy for Alzheimer disease.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 84 (3), 266-280, 2000

    公益社団法人 日本薬理学会

被引用文献 (2)*注記

もっと見る

参考文献 (78)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ