Antinociceptive and anti-inflammatory activity of a novel quipazine derivative (AAL-13): a selective inhibitor of 5-hydroxytryptamine reuptake

Abstract

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 measuring 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 < 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 < 0.05 and 103%, P < 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 < 0.05) and 86% (P < 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 < 0.02), 65% (P < 0.01) and 63% (P < 0.02), respectively. Intraperitoneally, only the 12 mg kg−1 dose produced significant inhibition (82%, 3 h after carrageenan injection, P < 0.05). AAL-13 (1.5 mg/ear) had a significant anti-inflammatory effect on the mouse ear (52%, inhibition, P < 0.05), while indomethacin (3 mg/ear) gave 43% inhibition (P < 0.05). AAL-13 raised the pain threshold and analgesic index in both inflamed and non-inflamed rat paw similarly, while indomethacin (2–3 mg kg−1) was more active in the inflamed paw. However, the larger dose of indomethacin (12 mg kg−1) did raise the threshold in non-inflamed limbs. AAL-13 (up to 100 mg kg−1 daily for 7 days) was devoid of any ulcerogenic effect on the stomach, while indomethacin was lethal in doses greater than 3 mg kg−1 daily. We postulated that the anti-inflammatory and antinociceptive activity of AAL-13 might be due to its ability to block 5-HT and noradrenaline reuptake.