Writhing test

Quite recently, a French group reported on the synthesis of 2-substituted 5-arylidene-pyridazinones as represented by the general formula (21, R1 = Ph, 2-ClC6H4 R2 = Ph(CH2)2, PhCO). These compounds were found to exhibit significant dose-dependent analgesic activity (phenylquinone-induced writhing test in mice oral administration) [92]. For a novel type of aminopyridazine-derived inhibitors of prostacyclin biosynthesis, see [93],... 

The 6-dimethylaminomethylpregna-3,5-diene (LVIIIb) is reported to be more active than pethidine in the mouse writhing test (EDso values are 8.4 and 24 mg/kg respectively) and to have significant analgesic properties in the hot... 

Table 5.6. WRITHING TEST ANALGESIA AND CLINICAL POTENCY [221]...

No. R r Form Antagonist activity AD50 value (mg/kg) Writhing test activity ED50 value (mg/kg)... 

The leaves of Aleurites moluccana contain 2"-C-rhamnosylswertisin and swertisin. The antinociceptive effect of both compounds was evaluated by the writhing test in mice. " The results indicated that the first derivative inhibits, dose dependently, the abdominal constrictions caused by acetic acid with an ID50 value of 6.9 to 10.2 pM/kg and maximal inhibition of 92%. When compared with aspirin ID5o= 133 pM/kg, the C-glycosylflavone was about 16-fold more potent. On the other hand, the swertisin alone did not show any effect. 

At present, BP 2.94 (36) is under clinical development in Phase II trials for the treatment of asthma, pneumoallergic diseases, and others. Preclinical studies in rodents clearly displayed anti-inflammatory as well as antinociceptive activity of BP 2.94 (36) given orally at low doses. These effects are mediated by inhibitory H3 receptors located on sensory C-fibres in several different tissues. In particular, capsaicin-induced plasma protein extravasation was dose-dependently inhibited in airways, digestive tract, skin, conjunctiva, urinaiy bladder, nasal mucosa, and dura mater of the rat. In the p-phenylbenzoquinone-induced writhing test in mice, BP 2.94 (36) had a pronounced antinociceptive activity similar to that of acetylsalicylic acid. This effect was significantly abolished by the H3 receptor antagonist thioperamide but not by naloxone. Furthermore, BP 2.94 (36) reduced zymosan-induced edema. This antiinflammatory effect was also abolished by thioperamide [6]. 

Other conformationally restricted forms of pethidine are the endo and exo isomeric azabicyclo[2,2,l]heptanes 30, which have similar orders of potency in mice (benzoquinone writhing test) after allowance is made for the greater ease with which the exo isomer penetrates the brain.(78) Reversed ester... 

Table 12.1. Writhing Test Analgesia and Clinical Potency"...

AD so and ED so analgesic and effective dose, respectively, necessary to elicit a 50% effect in mice after s.c. administration HP hot-plate test TF tail-flick test PPQ paraphenylquinone writhing test - not tested... 

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