Schane H P, Harding H R, Bell M R, Castracane V D, Winneker R C, Snyder B W
Steroids. 1985 Feb;45(2):171-85. doi: 10.1016/0039-128x(85)90046-7.
Six nonsteroidal phenylpyrazoles are described that have significant glucocorticoid and antiinflammatory activities. These agents competed with dexamethasone for the glucocorticoid receptor from the rat thymus, suppressed adrenal weight when administered orally to intact female rats, produced liver glycogen deposition and thymolysis when administered orally to adrenalectomized male rats, and reduced cotton granuloma formation when administered in the cotton pellet. In addition, in the latter model, no systemic activity (thymolysis or reduced body weight gain) was seen with doses up to 500 to 5000 times the dose which reduced granuloma formation. At least one compound was more potent than methylprednisolone in three of the four rat assay systems used. The compounds described are structurally different from conventional steroidal glucocorticoids but possessed potent glucocorticoid activities. However, they exhibited antiinflammatory activity without evidence of systemic activity when administered locally.
描述了六种具有显著糖皮质激素和抗炎活性的非甾体苯基吡唑。这些药物与地塞米松竞争大鼠胸腺中的糖皮质激素受体，口服给予完整雌性大鼠时可抑制肾上腺重量，口服给予去肾上腺雄性大鼠时可产生肝糖原沉积和胸腺溶解，在棉球肉芽肿模型中给药时可减少棉球肉芽肿形成。此外，在后者模型中，剂量高达减少肉芽肿形成剂量的500至5000倍时未观察到全身活性（胸腺溶解或体重增加减少）。在所使用的四种大鼠试验系统中的三种中，至少有一种化合物比甲泼尼龙更有效。所描述的化合物在结构上不同于传统的甾体糖皮质激素，但具有强大的糖皮质激素活性。然而，当局部给药时，它们表现出抗炎活性且无全身活性的证据。
