Inhibition of brain [(3)H]cimetidine binding by improgan-like antinociceptive drugs

Rebecca Stadel, Amanda B Carpenter, Julia W Nalwalk, Iwan J P de Esch, Elwin Janssen, Lindsay B Hough

Research output: Contribution to JournalArticleAcademicpeer-review


[(3)H]cimetidine, a radiolabeled histamine H(2) receptor antagonist, binds with high affinity to an unknown hemoprotein in the brain which is not the histamine H(2) receptor. Improgan, a close chemical congener of cimetidine, is a highly effective pain-relieving drug following CNS administration, yet its mechanism of action remains unknown. To test the hypothesis that the [(3)H]cimetidine-binding site is the improgan antinociceptive target, improgan, cimetidine, and 8 other chemical congeners were studied as potential inhibitors of [(3)H]cimetidine binding in membrane fractions from the rat brain. All compounds produced a concentration-dependent inhibition of [(3)H]cimetidine binding over a 500-fold range of potencies (K(i) values were 14.5 to >8000nM). However, antinociceptive potencies in rats did not significantly correlate with [(3)H]cimetidine-binding affinities (r=0.018, p=0.97, n=10). These results suggest that the [(3)H]cimetidine-binding site is not the analgesic target for improgan-like drugs.

Original languageEnglish
Pages (from-to)33-38
Number of pages6
JournalEuropean Journal of Pharmacology
Issue number1-3
Early online date6 Feb 2010
Publication statusPublished - 25 Apr 2010


  • Analgesics/chemistry
  • Animals
  • Binding Sites
  • Brain/metabolism
  • Cimetidine/analogs & derivatives
  • Dose-Response Relationship, Drug
  • Histamine/metabolism
  • Histamine H2 Antagonists/metabolism
  • Male
  • Molecular Structure
  • Pain/metabolism
  • Rats
  • Rats, Sprague-Dawley


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