Lack of activity of azapropazone in the hot-plate test and in 5-HT1A and 5-HT2 receptor subtypes in rat brain membranes.
This study aimed to investigate the antinociceptive activity of azapropazone (AZA), a weak prostaglandin synthesis inhibitor using the hot-plate test, and its ability to modify the serotonin-binding capacity in rat brain membranes. It revealed that AZA had no antinociceptive effect in the hot-plate test at the doses of 400 and 600 mg/kg when orally administered (p.o.), and at 400, 500 and 600 mg/kg after intraperitoneal injection (i.p.). At the dose of 600 mg/kg i.p. the drug failed to modify the number and the affinity of 5-HT1A and 5-HT2 receptors in rat brain membranes. In accordance with our previous findings on a positive correlation between NSAIDs antinociception in this experimental model and changes in 5-HT receptor characteristics, these results suggest an association between the lack of AZA-mediated antinociception in the hot-plate test and the drug's inability to modify the characteristics of 5-HT1A and 5-HT2 receptor binding sites in rat brain membranes.
Pini
L A
LA
Clinical Pharmacology Unit, University of Modena, Italy.
Sandrini
M
M
Vitale
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000493:pharmacokinetics; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology*; D001032:Apazone / Q000493:pharmacokinetics / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D007650:Ketanserin / Q000493:pharmacokinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D001032:Apazone