Anti-inflammatory and antinociceptive effects of 6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine in mice.

Abstract

BACKGROUND:

QUAN-0808 (6-(4-chlorophenoxy)-tetrazolo[5,1-a]phthalazine), a new phthalazine tetrazole derivative, was evaluated for the anti-inflammatory and analgesic effects.

METHODS:

Xylene-induced ear edema, carrageenan (Carr)-induced paw edema, and acetic acid-induced capillary permeability hyperactivity in mice were used to assess the anti-inflammatory effect; acetic acid-induced writhing and hot plate responses for the analgesic activity.

RESULTS:

In the present study, QUAN-0808 (100, 200, 400 mg/kg) and indomethacin (Indo) significantly decreased xylene-induced ear edema by 33.3, 37.5, 46.6, and 45.1%, respectively, decreased Carr-induced paw edema at 1, 2, 4 h after Carr injection, and decreased the prostaglandin E(2) (PGE(2)) and nitric oxide (NO) levels on the edema paw at 4 h after Carr injection; QUAN-0808 (100, 200, 400 mg/kg), and aspirin (Asp, 200 mg/kg) significantly decreased Evans blue exudation in acetic acid-induced capillary permeability hyperactivity model by 26.7, 28.7, 32.3 and 29.1%, respectively, and decreased the numbers of acetic acid-induced writhing response in 15 min by 40.4, 53.6, 66.4, and 64.5%, respectively. Morphine (10 mg/kg) significantly increased the latency of the hot plate response by 136.5, 117.4, 67.5, and 22.7%, respectively, at 30, 60, 90, 120 min after intraperitoneal injection of morphine; however, QUAN-0808 (100, 200 and 400 mg/kg) did not produce significantly antinociceptive effects in the hot plate test, suggesting that its antinociceptive action occurs via peripheral rather than a central-acting mechanism.

CONCLUSIONS:

These results show that QUAN-0808 produced potential anti-inflammatory and peripheral antinociceptive effects, and indicated that the antinociceptive effects of QUAN-0808 were related to its anti-inflammatory activity in a dose-dependent manner. Therefore, as inflammation is a peripheral process, it is suggested that QUAN-0808 exerted peripheral effects. The peripheral effect mechanisms of QUAN-0808 may be related to a decrease in the production of PGE(2), NO, bradykinin and other inflammatory mediators.

• Authors: Hai-Ling Yu, Feng Zhang, Ying-Jun Li, Guo-Hua Gong, Zhe-Shan Quan
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 64 Issue 5 Pg. 1155-65 ( 2012) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 23238472 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-(4-chlorophenoxy)tetrazolo(5,1-a)phthalazine
• Analgesics
• Anti-Inflammatory Agents
• Phthalazines
• Tetrazoles
• Xylenes
• Nitric Oxide
• Dinoprostone

Topics

• Analgesics (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Dinoprostone (analysis)
• Male
• Mice
• Nitric Oxide (physiology)
• Peritonitis (drug therapy)
• Phthalazines (pharmacology)
• Tetrazoles (pharmacology)
• Xylenes (pharmacology)