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Cheming Teng - One of the best experts on this subject based on the ideXlab platform.
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effect of anti inflammatory drugs on the cardiotoxin induced Hind Paw oedema in rats
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Jihpyang Wang, Cheming TengAbstract:— Cardiotoxin, isolated from Naja naja atra venom, induced rat Hind-Paw oedema. This effect was suppressed by the pretreatment with dexamethasone or BW 755C, or subplantar co-injection with FPL 55712. Pretreatment with aspirin alone did not affect this response, while a significant reduction of cardiotoxin-induced Paw oedema was achieved with aspirin in combination with diphenhydramine and methysergide. Subplantar co-injection of PAF antagonist, BN 52021 or L 652731, with cardiotoxin had no effect on Paw oedema, whereas superoxide dismutase/catalase reduced this oedematous response. Cardiotoxin-induced Paw oedema was also suppressed by pretreating the rats with isoprenaline. Pretreatment with rat anti-platelet plasma, which greatly reduced peripheral platelet count, did not affect cardiotoxin-induced Paw oedema. Cardiotoxin did not trigger platelet aggregation or release reaction either in platelet-rich plasma or in washed platelet suspension. The oedematous response after subplantar co-injection of cardiotoxin with basic or acidic phospholipase A2 appeared to be only an additive effect. These results suggest that arachidonate metabolites, in which leukotrienes are most important, participated in cardiotoxin-induced Paw oedema. Superoxide radical was also involved, while PAF and platelets showed little influence in this oedema effect.
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roles of pmn leucocytes platelets and some mediators in rat Hind Paw oedema induced by two phospholipase a2 enzymes from trimeresurus mucrosquamatus venom
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Jihpyang Wang, Cheming TengAbstract:Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimeresurus mucrosquamatus venom induced rat Hind-Paw oedema. Recovered myeloperoxidase activity increased within 1 h and was greatly elevated in the rat Paw 3-6 h after subplantar injection of these venom PLA2 enzymes. Methotrexate pretreatment significantly reduced not only the peripheral leucocyte count but also venom PLA2-induced Paw oedema. In rat isolated PMN leucocyte suspension, venom PLA2 induced superoxide radical formation. Paw swelling caused by TMVPLA2 I or TMVPLA2 II was only slightly or not, respectively, reduced in the rats pretreated with anti-platelet plasma, which reduced peripheral blood platelet count by greater than 96%, suggesting platelets are not involved. In isolated platelet preparation, TMVPLA2 I induced platelet activation in a concentration-dependent manner, while TMVPLA2 II had no effect. Pretreatment with diphenhydramine/methysergide greatly suppressed the oedematous responses caused by the two venom PLA2 enzymes; the residual responses were significantly further depressed by aspirin. The oedematous responses caused by the enzymes were also suppressed by FPL 55712, BW 755C, dexamethasone, superoxide dismutase/catalase, isoprenaline and terbutaline. However, BN 52021 and L 652731, both platelet aggregating factor antagonists, were not effective on these responses. Thus, in addition to histamine and 5-hydroxytryptamine release by the mast cells in PLA2-induced Paw oedema (Wang & Teng 1990), the results of this study indicate minor, but significant, roles for neutrophils and inflammatory mediators including prostaglandins, leukotrienes and superoxide radicals.
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effects of anti inflammatory drugs on rat Hind Paw swelling caused by phospholipase a2 from naja naja atra venom
Naunyn-schmiedebergs Archives of Pharmacology, 1991Co-Authors: Jihpyang Wang, Cheming TengAbstract:Rat Hind-Paw swelling was induced dose-dependently by subplantar injection of acidic phospholipase A2 (NNAVPLA2) from Naja naja atra venom. Diphenhydramine and methysergide pretreatment greatly reduced the swelling effect caused by NNAVPLA2. Several doses of compound 48/80 given to deplete the histamine content of rat Hind Paw, also greatly suppressed NNAVPLA2-induced Paw swelling. The Paw swelling caused by NNAVPLA2 was reduced following pretreatment with BW 755C, a dual inhibitor of cyclooxygenase/lipoxygenase, or subplantar co-injection with FPL 55712, a SRS-A antagonist, while pretreatment with acetylsalicylic acid had no effect. Captopril significantly potentiated the NNAVPLA2-induced Paw swelling. The recovered myeloperoxidase activity was increased within 1 h and still elevated in the rat Paw 3 to 6 h after subplantar injection of NNAVPLAZ. In isolated peripheral PMN leukocyte suspension, NNAVPLAZ caused a release of superoxide radical. Subplantar co-injection with superoxide dismutase/catalase significantly inhibited NNAVPLA2-induced Paw swelling. NNAVPLA2 did not trigger platelet aggregation either in platelet-rich plasma or in washed platelet suspension. NNAVPLA2-induced Hind-Paw swelling was also suppressed by the pretreatment with isoprenaline or terbutaline, while this response was not affected by co-injection with BN 52021, a PAF antagonist, into the Paw. It is concluded that the HindPaw swelling caused by NNAVPLAZ is mainly due to histamine and serotonin released from mast cells and partly due to the formed kinins and SRS-A in the inflammatory area, and superoxide radical from PMN leukocytes.
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Rat Hind-Paw swelling effect of an edema-producing protein isolated from Trimeresurus mucrosquamatus snake venom
Naunyn-Schmiedeberg's Archives of Pharmacology, 1991Co-Authors: Jihpyang Wang, Hui-chin Peng, Cheming TengAbstract:TMV F-IV, isolated from the venom of Trimeresurus mucrosquamatus (TMV), caused rat HindPaw edema in a dose-dependent manner. The maximum Hind-Paw swelling was reached at 1:5—2 h after subplantar injection of TMV F-IV. The edematous response caused by TMV F-IV was suppressed by the s.c. pretreatment with diphenhydramine, methysergide, acetylsalicylic acid or dexamethasone, and by the subplantar co-injection with FPL 55712, a SRS-A antagonist, and BN 52021 or L 652731, both PAF antagonists. Polymorphonuclear (PMN) leukocyte infiltration appeared within 1 h and gradually increased in the rat Paw 3–6 h after edema induction. Compound 48/80 or methotrexate pretreatment also inhibited Paw edema caused by TMV F-IV. In isolated mast cells, TMV F-IV increased the formation of PGE_2 and LTB_4 and caused a dose-dependent release of histamine and β-glucuronidase. Since there are no significant differences in Paw edema and mast cell degranulation responses between TMV F-IV and its DFP-modified analogue, the esterase activity may not be necessary in these models. These results indicate that mast cells, PMN leukocytes and some inflammatory mediators such as histamine, serotonin, arachidonate metabolites and PAF are involved in TMV F-IV induced Paw edema.
Jihpyang Wang - One of the best experts on this subject based on the ideXlab platform.
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effect of anti inflammatory drugs on the cardiotoxin induced Hind Paw oedema in rats
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Jihpyang Wang, Cheming TengAbstract:— Cardiotoxin, isolated from Naja naja atra venom, induced rat Hind-Paw oedema. This effect was suppressed by the pretreatment with dexamethasone or BW 755C, or subplantar co-injection with FPL 55712. Pretreatment with aspirin alone did not affect this response, while a significant reduction of cardiotoxin-induced Paw oedema was achieved with aspirin in combination with diphenhydramine and methysergide. Subplantar co-injection of PAF antagonist, BN 52021 or L 652731, with cardiotoxin had no effect on Paw oedema, whereas superoxide dismutase/catalase reduced this oedematous response. Cardiotoxin-induced Paw oedema was also suppressed by pretreating the rats with isoprenaline. Pretreatment with rat anti-platelet plasma, which greatly reduced peripheral platelet count, did not affect cardiotoxin-induced Paw oedema. Cardiotoxin did not trigger platelet aggregation or release reaction either in platelet-rich plasma or in washed platelet suspension. The oedematous response after subplantar co-injection of cardiotoxin with basic or acidic phospholipase A2 appeared to be only an additive effect. These results suggest that arachidonate metabolites, in which leukotrienes are most important, participated in cardiotoxin-induced Paw oedema. Superoxide radical was also involved, while PAF and platelets showed little influence in this oedema effect.
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roles of pmn leucocytes platelets and some mediators in rat Hind Paw oedema induced by two phospholipase a2 enzymes from trimeresurus mucrosquamatus venom
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Jihpyang Wang, Cheming TengAbstract:Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimeresurus mucrosquamatus venom induced rat Hind-Paw oedema. Recovered myeloperoxidase activity increased within 1 h and was greatly elevated in the rat Paw 3-6 h after subplantar injection of these venom PLA2 enzymes. Methotrexate pretreatment significantly reduced not only the peripheral leucocyte count but also venom PLA2-induced Paw oedema. In rat isolated PMN leucocyte suspension, venom PLA2 induced superoxide radical formation. Paw swelling caused by TMVPLA2 I or TMVPLA2 II was only slightly or not, respectively, reduced in the rats pretreated with anti-platelet plasma, which reduced peripheral blood platelet count by greater than 96%, suggesting platelets are not involved. In isolated platelet preparation, TMVPLA2 I induced platelet activation in a concentration-dependent manner, while TMVPLA2 II had no effect. Pretreatment with diphenhydramine/methysergide greatly suppressed the oedematous responses caused by the two venom PLA2 enzymes; the residual responses were significantly further depressed by aspirin. The oedematous responses caused by the enzymes were also suppressed by FPL 55712, BW 755C, dexamethasone, superoxide dismutase/catalase, isoprenaline and terbutaline. However, BN 52021 and L 652731, both platelet aggregating factor antagonists, were not effective on these responses. Thus, in addition to histamine and 5-hydroxytryptamine release by the mast cells in PLA2-induced Paw oedema (Wang & Teng 1990), the results of this study indicate minor, but significant, roles for neutrophils and inflammatory mediators including prostaglandins, leukotrienes and superoxide radicals.
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inhibition of Hind Paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin
European Journal of Pharmacology, 1995Co-Authors: Jihpyang Wang, Shueling Raung, Lingchu ChangAbstract:Abstract Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced Hind-Paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal Hind-Paw skin by antidromic stimulation of the saphenous nerve, and in passive cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48 80 -, histamine- and serotonin-induced ear edema. Indomethacin was ineffective in these respects. Bradykinin- and substance P-induced plasma exudation were also significantly reduced when [Thi5,8, d -Phe7]bradykinin and [ d -Pro2, d -Trp7,9]substance P were coinjected with bradykinin and substance P, respectively. In isolated rat peritoneal mast cell preparation, acetylshikonin produced a concentration-dependent inhibition of histamine and β-glucuronidase release from mast cells challenged by compound 48 80 . In compound 48 80 - pretreated mice, acetylshikonin and isoproterenol produced significantly more inhibitory effect on bradykinin- and substance P-induced plasma exudation than did diphenhydramine in combination with methysergide. Pretreatment with diphenhydramine/methysergide in compound 48 80 - pretreated mice significantly further reduced the bradykinin- and substance P-induced plasma exudation if [Thi5,8, d -Phe7]bradykinin and [ d -Pro2, d -Trp7,9]substance P were coinjected with bradykinin or substance P, respectively. The results suggest that the inhibitory effect of acetylshikonin on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge.
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suppressive effect of 2 phenyl 4 quinolone yt 1 on Hind Paw edema and cutaneous vascular plasma extravasation in mice
Naunyn-schmiedebergs Archives of Pharmacology, 1994Co-Authors: Jihpyang Wang, Shueling Raung, Meifeng Hsu, Shengchu KuoAbstract:Like indomethacin, BW755C, diphenhydramine and methysergide, 2-phenyl-4-quinolone (YT-1) suppressed the polymyxin B-induced Hind-Paw edema. This inhibitory effect of YT-1 was also demonstrated in adrenalectomized mice. YT-1 inhibited the antidromic stimulation of saphenous nerve-induced plasma leakage in dorsal Paw skin and reduced the volume of plasma exudation in PCA reaction. Bradykinin-, substance P- and compound 48/80-induced mouse ear edema was suppressed by YT-1 in a dose-dependent manner. In isolated rat peritoneal mast cells, YT-1 produced a dose-dependent inhibition of bradykinin-, substance P- and compound 48/80-induced histamine and β-glucuronidase release. YT-1 also reduced the TXB2 formation from PMN leukocytes with IC50 2.0±0.5 μM, however with little effect on LTB4 formation. Histamine- and serotonin-induced plasma exudation in ear edema were reduced by YT-1. Moreover, the maximal response of ileum contraction caused by histamine and serotonin were also suppressed by YT-1 in a dose-dependent manner. In compound 48/80-pretreatment mice, YT-1 failed to suppress the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These results indicate that the inhibitory effect of YT-1 on local edema formation is not through the release of steroid hormones from adrenal gland, and is probably by suppressing the release of chemical mediators from mast cells, inhibition of prostaglandins formation, and noncompetitive but selective protection of the vasculature against the histamine- and serotonin-induced plasma extravasation.
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effects of anti inflammatory drugs on rat Hind Paw swelling caused by phospholipase a2 from naja naja atra venom
Naunyn-schmiedebergs Archives of Pharmacology, 1991Co-Authors: Jihpyang Wang, Cheming TengAbstract:Rat Hind-Paw swelling was induced dose-dependently by subplantar injection of acidic phospholipase A2 (NNAVPLA2) from Naja naja atra venom. Diphenhydramine and methysergide pretreatment greatly reduced the swelling effect caused by NNAVPLA2. Several doses of compound 48/80 given to deplete the histamine content of rat Hind Paw, also greatly suppressed NNAVPLA2-induced Paw swelling. The Paw swelling caused by NNAVPLA2 was reduced following pretreatment with BW 755C, a dual inhibitor of cyclooxygenase/lipoxygenase, or subplantar co-injection with FPL 55712, a SRS-A antagonist, while pretreatment with acetylsalicylic acid had no effect. Captopril significantly potentiated the NNAVPLA2-induced Paw swelling. The recovered myeloperoxidase activity was increased within 1 h and still elevated in the rat Paw 3 to 6 h after subplantar injection of NNAVPLAZ. In isolated peripheral PMN leukocyte suspension, NNAVPLAZ caused a release of superoxide radical. Subplantar co-injection with superoxide dismutase/catalase significantly inhibited NNAVPLA2-induced Paw swelling. NNAVPLA2 did not trigger platelet aggregation either in platelet-rich plasma or in washed platelet suspension. NNAVPLA2-induced Hind-Paw swelling was also suppressed by the pretreatment with isoprenaline or terbutaline, while this response was not affected by co-injection with BN 52021, a PAF antagonist, into the Paw. It is concluded that the HindPaw swelling caused by NNAVPLAZ is mainly due to histamine and serotonin released from mast cells and partly due to the formed kinins and SRS-A in the inflammatory area, and superoxide radical from PMN leukocytes.
Naoki Ohara - One of the best experts on this subject based on the ideXlab platform.
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antiinflammatory effect of topically applied propolis extract in carrageenan induced rat Hind Paw edema
Phytotherapy Research, 2007Co-Authors: Yukiko Naito, Misao Yasumuro, Keiichiro Kondou, Naoki OharaAbstract:The antiinflammatory effect of an ointment containing propolis extract (3%–7%) was examined using carrageenan-induced Hind Paw edema in rats. Treatment with the ointment inhibited the edema moderately, and the inhibition was significant at 5% and 7%. Additionally, the effect of the ointment on chemotaxis of human polymorphonuclear leukocytes (PMNs) was investigated using the agarose plate method. Migration of PMNs toward zymosan-treated serum was inhibited in the presence of 5% propolis ointment. These results demonstrate that topical application of propolis extract is effective in inhibiting carrageenan-induced rat Hind Paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the antiinflammatory effect. Copyright © 2007 John Wiley & Sons, Ltd.
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antiinflammatory effect of topically applied propolis extract in carrageenan induced rat Hind Paw edema
Phytotherapy Research, 2007Co-Authors: Yukiko Naito, Misao Yasumuro, Keiichiro Kondou, Naoki OharaAbstract:The antiinflammatory effect of an ointment containing propolis extract (3%-7%) was examined using carrageenan-induced Hind Paw edema in rats. Treatment with the ointment inhibited the edema moderately, and the inhibition was significant at 5% and 7%. Additionally, the effect of the ointment on chemotaxis of human polymorphonuclear leukocytes (PMNs) was investigated using the agarose plate method. Migration of PMNs toward zymosan-treated serum was inhibited in the presence of 5% propolis ointment. These results demonstrate that topical application of propolis extract is effective in inhibiting carrageenan-induced rat Hind Paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the antiinflammatory effect.
Yukiko Naito - One of the best experts on this subject based on the ideXlab platform.
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antiinflammatory effect of topically applied propolis extract in carrageenan induced rat Hind Paw edema
Phytotherapy Research, 2007Co-Authors: Yukiko Naito, Misao Yasumuro, Keiichiro Kondou, Naoki OharaAbstract:The antiinflammatory effect of an ointment containing propolis extract (3%–7%) was examined using carrageenan-induced Hind Paw edema in rats. Treatment with the ointment inhibited the edema moderately, and the inhibition was significant at 5% and 7%. Additionally, the effect of the ointment on chemotaxis of human polymorphonuclear leukocytes (PMNs) was investigated using the agarose plate method. Migration of PMNs toward zymosan-treated serum was inhibited in the presence of 5% propolis ointment. These results demonstrate that topical application of propolis extract is effective in inhibiting carrageenan-induced rat Hind Paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the antiinflammatory effect. Copyright © 2007 John Wiley & Sons, Ltd.
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antiinflammatory effect of topically applied propolis extract in carrageenan induced rat Hind Paw edema
Phytotherapy Research, 2007Co-Authors: Yukiko Naito, Misao Yasumuro, Keiichiro Kondou, Naoki OharaAbstract:The antiinflammatory effect of an ointment containing propolis extract (3%-7%) was examined using carrageenan-induced Hind Paw edema in rats. Treatment with the ointment inhibited the edema moderately, and the inhibition was significant at 5% and 7%. Additionally, the effect of the ointment on chemotaxis of human polymorphonuclear leukocytes (PMNs) was investigated using the agarose plate method. Migration of PMNs toward zymosan-treated serum was inhibited in the presence of 5% propolis ointment. These results demonstrate that topical application of propolis extract is effective in inhibiting carrageenan-induced rat Hind Paw edema, and its inhibitory effect on the chemotaxis of PMNs may also contribute to the antiinflammatory effect.
Barbara Costa - One of the best experts on this subject based on the ideXlab platform.
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inhibitors of fatty acid amide hydrolase reduce carrageenan induced Hind Paw inflammation in pentobarbital treated mice comparison with indomethacin and possible involvement of cannabinoid receptors
British Journal of Pharmacology, 2005Co-Authors: Sandra Holt, Francesca Comelli, Barbara CostaAbstract:The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced Hind Paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice. Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg(-1)) 30 min prior to carrageenan administration, dose-dependently reduced oedema formation. At the 4 h time point, the ED(50) for URB597 was approximately 0.3 mg kg(-1). Indomethacin (5 mg kg(-1) i.p.) completely prevented the oedema response to carrageenan. The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg(-1) i.p. of the CB(2) receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator-activated receptor gamma antagonist bisphenol A diglycidyl ether (30 mg kg(-1) i.p.) or the TRPV1 antagonist capsazepine (10 mg kg(-1) i.p.), when oedema was assessed 4 h after carrageenan administration. The CB(1) receptor antagonists AM251 (3 mg kg(-1) i.p.) and rimonabant (0.5 mg kg(-1) i.p.) gave inconsistent effects upon the antioedema effect of URB597. FAAH measurements were conducted ex vivo in the Paws, spinal cords and brains of the mice. The activities of FAAH in the Paws and spinal cords of the inflamed vehicle-treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg(-1)) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528-sensitive anti-inflammatory effects in the carrageenan model of acute inflammation.
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inhibitors of fatty acid amide hydrolase reduce carrageenan induced Hind Paw inflammation in pentobarbital treated mice comparison with indomethacin and possible involvement of cannabinoid receptors
British Journal of Pharmacology, 2005Co-Authors: Sandra Holt, Francesca Comelli, Barbara Costa, Christopher J FowlerAbstract:The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced Hind Paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice. Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg−1) 30 min prior to carrageenan administration, dose-dependently reduced oedema formation. At the 4 h time point, the ED50 for URB597 was ∼0.3 mg kg−1. Indomethacin (5 mg kg−1 i.p.) completely prevented the oedema response to carrageenan. The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg−1 i.p. of the CB2 receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator-activated receptor γ antagonist bisphenol A diglycidyl ether (30 mg kg−1 i.p.) or the TRPV1 antagonist capsazepine (10 mg kg−1 i.p.), when oedema was assessed 4 h after carrageenan administration. The CB1 receptor antagonists AM251 (3 mg kg−1 i.p.) and rimonabant (0.5 mg kg−1 i.p.) gave inconsistent effects upon the antioedema effect of URB597. FAAH measurements were conducted ex vivo in the Paws, spinal cords and brains of the mice. The activities of FAAH in the Paws and spinal cords of the inflamed vehicle-treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg−1) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments. In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528-sensitive anti-inflammatory effects in the carrageenan model of acute inflammation. Keywords: Endocannabinoid, fatty acid amide hydrolase, URB597, indomethacin, SR144528, carrageenan, inflammation Introduction There is evidence to suggest that compounds affecting the endogenous cannabinoid (‘endocannabinoid') system may have therapeutic usefulness in a number of areas, including stroke, multiple sclerosis, pain and inflammation (see Pertwee, 2002; Rice et al., 2002; Croxford, 2003; Fowler, 2004 for recent reviews). The endocannabinoids, of which the two most well investigated are anandamide (arachidonoylethanolamide, AEA) and 2-arachidonoyl glycerol, are synthesised on demand (see Bisogno et al., 2005; Lambert & Fowler, 2005), and exert most of their effects by actions upon cannabinoid CB1 and CB2 receptors (Devane et al., 1988; Munro et al., 1993) and (for AEA) the transient receptor potential vanilloid type 1 receptors (TRPV1) (Zygmunt et al., 1999). The actions of the endocannabinoids are terminated by their rapid removal through uptake and intracellular degradation (see Bisogno et al., 2005; Lambert & Fowler, 2005). Inhibition of endocannabinoid metabolism is considered a promising therapeutic target on its own, since it presumably would increase the endocannabinoid level only at the location where their synthesis has been stimulated, but also in combination with exogenous AEA, prolonging its availability. AEA is metabolised mainly by the enzyme fatty acid amide hydrolase (FAAH), producing arachidonic acid and ethanolamine (Deutsch & Chin, 1993) and also by other enzymes, including cyclooxygenase-2 (COX-2), producing prostaglandin-ethanolamides, also called prostamides (Yu et al., 1997). Although a number of compounds have been shown to inhibit FAAH, including the serine protease inhibitor phenylmethylsulphonyl fluoride (PMSF, Deutsch & Chin, 1993) and a number of nonsteroidal anti-inflammatory drugs (NSAIDs) including indomethacin and flurbiprofen (Paria et al., 1996; Fowler et al., 2003), it is only in recent years that selective compounds have been identified. Thus, for example, the carbamate compound URB597 (3′-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) shows good selectivity for FAAH vs other targets such as CB receptors and monoacylglycerol lipase, the main catabolic enzyme for 2-arachidonoyl glycerol in the brain (Kathuria et al., 2003). These authors demonstrated further that this compound produced potentially important effects in a model of anxiety (the elevated plus maze in the rat) as well as antinociceptive effects in the mouse hotplate test (Kathuria et al., 2003). URB597 also reduces, in a manner blocked by a CB1 (but not a CB2) receptor antagonist, established inflammatory pain in the rat produced by prior intraplantar (i.pl.) injection of Freund's complete adjuvant (Wilson et al., 2005). Other selective FAAH inhibitors have been reported to produce analgesic effects (Lichtman et al., 2004a) and to have potentially beneficial effects upon tumour cell growth (Bifulco et al., 2004). In two recent studies, it was reported that genetic deletion of either all FAAH (Lichtman et al., 2004b) or only peripheral FAAH (Cravatt et al., 2004) produced mice that were less sensitive to the inflammatory effects of local administration of carrageenan into the Hind Paw. Genetic ablation of FAAH also produces protection against intestinal inflammation (Massa et al., 2004). It would be useful to know whether such effects can also be produced by pharmacological inhibition of FAAH. In the present study, the abilities of URB597 and PMSF to inhibit carrageenan-induced oedema have been investigated and compared with indomethacin, a standard NSAID known to produce robust effects in this model (see e.g. Siqueira-Junior et al., 2003). In addition, CB receptor antagonists have been used in an attempt to elucidate whether the endocannabinoid system is involved in the anti-inflammatory effects of these compounds. A report of some of the present data was presented to the 2004 Meeting of the International Cannabinoid Research Society in June of that year (abstract published, Holt et al., 2004a).