ANTINOCICEPTIVE AND ANTIINFLAMMATORY ACTIVITY OF A NOVEL QUIPAZINE DERIVATIVE (AAL-13) - A SELECTIVE INHIBITOR OF 5-HYDROXYTRYPTAMINE REUPTAKE

被引:3
作者
ELMAHDY, SAM
ALHAIDER, AA
MAHGOUB, AA
机构
[1] Department of Medical Pharmacology, College of Medicine, King Saud University, Riyadh, 11495
关键词
D O I
10.1111/j.2042-7158.1990.tb06613.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. 1990 Royal Pharmaceutical Society of Great Britain
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页码:522 / 524
页数:3
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