Improgan antinociception does not require neuronal histamine or histamine receptors

Jalal Izadi Mobarakeh, Julia W. Nalwalk, Takeshi Watanabe, Shinobu Sakurada, Marcel Hoffman, Rob Leurs, Henk Timmerman, Immaculada Silos-Santiago, Kazuhiko Yanai, Lindsay B. Hough

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Improgan, a chemical congener of the H2 antagonist cimetidine, induces antinociception following intracerebroventricular (i.c.v.) administration in rodents, but the mechanism of action of this compound remains unknown. Because the chemical structure of improgan closely resembles those of histamine and certain histamine blockers, and because neuronal histamine is known to participate in pain-relieving responses, the antinociceptive actions of improgan were evaluated in mice containing null mutations in the genes for three histamine receptors (H1, H2, and H3) and also in the gene for histidine decarboxylase (the histamine biosynthetic enzyme). Similar to earlier findings in Swiss-Webster mice, improgan induced maximal, reversible, dose-related reductions in thermal nociceptive responses in ICR mice, but neither pre-improgan (baseline) nor post-improgan nociceptive latencies were changed in any of the mutant mice as compared with wild-type controls. Improgan also had weak inhibitory activity in vitro (pKi=4.7-4.9) on specific binding to three recently-discovered, recombinant isoforms of the rat H3 receptor (H3A, H3B, and H3C). The present findings strongly support the hypothesis that neuronal histamine and its receptors fail to play a role in improgan-induced antinociception.

Original languageEnglish
Pages (from-to)146-152
Number of pages7
JournalBrain research
Issue number1-2
Publication statusPublished - 2003 Jun 6


  • Analgesia
  • Antinociception
  • Cimetidine
  • Histamine
  • Improgan

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology


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