Antinociceptive and anti-inflammatory activity of a novel quipazine derivative (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake.
The anti-inflammatory and antinociceptive activities of a novel quipazine derivative 2(4-(3-chloropropyl)piperazinyl) quinoline (AAL-13), a selective inhibitor of 5-hydroxytryptamine (5-HT) reuptake, has been examined. Anti-inflammatory activity was assessed by mesuring the inhibition of a cotton pellet granuloma and of carrageenan-induced paw oedema in rats, and of cantharidin-induced topical inflammation in the mouse ear. Antinociceptive activity was studied by using the modified Randall-Selitto method. Indomethacin was used as a reference. AAL-13 slightly inhibited granuloma formation (13%, P less than 0.02) at 100 mg kg-1 day-1 for 7 days, whereas half that dose had no significant effect. There was significant inhibition of carrageenan-induced rat paw oedema (35%, P less than 0.05 and 103%, P less than 0.001) 3 h after single doses of AAL-13 (50 and 100 mg kg-1 p.o., respectively). Three hours after i.p. injection, the oedema inhibition was 58% (P less than 0.05) and 86% (P less than 0.001) for doses of 25 and 50 mg kg-1, respectively. In comparison, indomethacin (3, 6 and 12 mg kg-1 p.o.) inhibited oedema by 59% (P less than 0.02), 65% (P less than 0.01) and 63% (P less than 0.02), respectively. Intraperitoneally, only the 12 mg kg-1 dose produced significant inhibition (82%, 3 h after carrageenan injection, P less than 0.05). AAL-13 (1.5 mg/ear) had a significant anti-inflammatory effect on the mouse ear (52%, inhibition, P less than 0.05), while indomethacin (3 mg/ear) gave 43% inhibition (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
el-Mahdy
S A
SA
Department of Medical Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Alhaider
A A
AA
Mahgoub
A A
AA
D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D011814:Quipazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology* / Q000627:therapeutic use
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D012702:Serotonin Antagonists; C067011:2-(4-(3-chloropropyl)piperazinyl)quinoline; D011814:Quipazine; D007213:Indomethacin