Abdel-Salam Omar M E, Baiuomy Ayman R, Arbid Mahmoud S
Department of Pharmacology, National Research Centre, Tahrir Street, Dokki, Cairo, Egypt.
Pharmacol Res. 2004 Feb;49(2):119-31. doi: 10.1016/j.phrs.2003.07.016.
The anti-inflammatory activity of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), was studied on the carrageenan-induced paw inflammation in the rat. Fluoxetine (10-60 mg kg(-1)) given intraperitoneally (i.p.) 30 min before carrageenan, displayed marked anti-inflammatory activity, inhibiting paw oedema by 38.6-77.7% at 2 h post-carrageenan. Fluoxetine administered at time of carrageenan injection or 30 min after carrageenan challenge, markedly inhibited the paw oedema response. Rats administered daily fluoxetine (20 mg kg(-1), i.p.) showed significantly decreased inflammatory response to subplantar carrageenan when examined on the 5th and 14th day of fluoxetine injection. Fluoxetine (10 or 20 mg kg(-1), i.p.) co-administered with indomethacin (IND) (20 mg kg(-1), i.p.), celecoxib (10 mg kg(-1), i.p.) or rofecoxib (4.5 mg kg(-1), i.p.) before carrageenan reduced the anti-oedema effect of indomethacin or celecoxib, but had additive effect to that of rofecoxib. The anti-oedema effects of fluoxetine and melatonin or the tricyclic antidepressant imipramine were additive. In contrast, administration of both fluoxetine and the heterocyclic antidepressant trazodone had no greater anti-inflammatory effect than fluoxetine alone. The anti-oedema effect of fluoxetine was partially suppressed by the opioid antagonist naloxone (4 mg kg(-1), i.p.). Fluoxetine (360 or 720 microg per paw) given into the rat paw with carrageenan reduced the oedema response by 25.4 and 35.3% 4 h post-carrageenan, respectively. It is suggested that fluoxetine alone or co-administered with either imipramine or melatonin would be of benefit in the sitting of neuropathic or inflammatory pain conditions. Both the serotonergic and the opioid systems are likely to be involved in the modulating action of fluoxetine on peripheral inflammation.
在大鼠角叉菜胶诱导的爪部炎症模型上，研究了选择性5-羟色胺再摄取抑制剂（SSRI）氟西汀的抗炎活性。在注射角叉菜胶前30分钟腹腔注射氟西汀（10 - 60毫克/千克），表现出显著的抗炎活性，在注射角叉菜胶后2小时，抑制爪部水肿38.6% - 77.7%。在注射角叉菜胶时或注射角叉菜胶后30分钟给予氟西汀，能显著抑制爪部水肿反应。在氟西汀注射第5天和第14天检查时，每天腹腔注射氟西汀（20毫克/千克）的大鼠对足底注射角叉菜胶的炎症反应显著降低。在注射角叉菜胶前，氟西汀（10或20毫克/千克，腹腔注射）与吲哚美辛（IND）（20毫克/千克，腹腔注射）、塞来昔布（10毫克/千克，腹腔注射）或罗非昔布（4.5毫克/千克，腹腔注射）联合使用，可降低吲哚美辛或塞来昔布的抗水肿作用，但与罗非昔布有相加作用。氟西汀与褪黑素或三环类抗抑郁药丙咪嗪的抗水肿作用是相加的。相反，同时给予氟西汀和杂环类抗抑郁药曲唑酮并不比单独使用氟西汀有更强的抗炎作用。氟西汀的抗水肿作用部分被阿片受体拮抗剂纳洛酮（4毫克/千克，腹腔注射）抑制。将氟西汀（每爪360或720微克）与角叉菜胶一起注射到大鼠爪部，在注射角叉菜胶后4小时，水肿反应分别降低25.4%和35.3%。提示单独使用氟西汀或与丙咪嗪或褪黑素联合使用可能有助于治疗神经性或炎症性疼痛。5-羟色胺能系统和阿片系统可能都参与了氟西汀对外周炎症的调节作用。
