Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 357, Issue 5, pp 508–513

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice

  • K. Onodera
  • Shuichi Miyazaki
  • Masahiro Imaizumi
  • Holger Stark
  • Walter Schunack
Original article

DOI: 10.1007/PL00005200

Cite this article as:
Onodera, K., Miyazaki, S., Imaizumi, M. et al. Naunyn-Schmiedeberg's Arch Pharmacol (1998) 357: 508. doi:10.1007/PL00005200

Abstract

Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5 mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-—methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg, i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor antagonist with poor penetration of the blood-brain barrier, or zolantidine (20 mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a biochemical study, FUB 181 had no significant effect on either acetylcholine or choline level in mice brain at the doses tested. These findings suggest that FUB 181 increases the release of histamine by blocking presynaptic histamine H3 autoreceptors, and that released histamine in turn activates postsynaptic H1 and H2 receptors, predominantly histamine H1 receptors, and in this fashion improves learning and memory in mice. Our findings also suggest that the histaminergic system may play an important role in learning and memory, and that FUB 181 may be a clinical candidate for the therapy of dementia.

Key words Histamine histamine H3 receptor FUB 181 Learning and memory Elevated plus-maze test 

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • K. Onodera
    • 1
  • Shuichi Miyazaki
    • 2
  • Masahiro Imaizumi
    • 2
  • Holger Stark
    • 3
  • Walter Schunack
    • 3
  1. 1.Department of Pharmacology, Tohoku University School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980, JapanJP
  2. 2.Biology Laboratory, Yamasa Corporation, 10-1, Araoi-cho 2-chome, Choshi, Chiba 288, JapanJP
  3. 3.Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Strasse 2+4, D-14195 Berlin, GermanyDE

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