Abstract
[(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 language | English |
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Pages (from-to) | 33-38 |
Number of pages | 6 |
Journal | European Journal of Pharmacology |
Volume | 632 |
Issue number | 1-3 |
Early online date | 6 Feb 2010 |
DOIs | |
Publication status | Published - 25 Apr 2010 |
Keywords
- 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