Tsuji M, Saita M, Soejima Y, Takamori M, Noda K, Ueki S, Fujiwara M
Nihon Yakurigaku Zasshi. 1980 Nov;76(8):675-84.
Anti-carrageenin paw edema effects of 1-(m-trifluoromethylphenyl)-3-(2-hydroxyethyl)-quinazoline-2, 4(1H, 3H)-dione [H-88] and 1-(m-trifluoromethylphenyl)-3-ethylpyridopyrimidine-2, 4(1H, 3H)-dione [HN-37] in rats were dissipated or reduced markedly by adrenalectomy. The effects of both compounds on the pituitary-adrenal axis were therefore investigated in male Wistar rats at 5-6 weeks of age. Oral treatments with H-88 in a dose of 100 mg/kg and HN-37 at 10 mg/kg induced the same degree of responses in intact animals, namely, a marked increase of blood corticosterone level at one hr of the peak time (360%), a decrease of adrenal ascorbic acid level at 3 hr (52-59%), an increase of blood glucose level at 6-12 hr (25-59%) and of liver glycogen level at 12-4 hr (97-153%). In addition, a significant hypertrophy of the pituitary and adrenals (p less than 0.05) at 6-12 hr and/or atrophy of the thymus and spleen at 3-24 hr were noted. The effect of HN-37 on blood corticosterone level was approximately 10 times as potent as that of H-88 as well as on the carrageenin paw edema. The effects of both compounds on blood corticosterone level were dissipated by adrenalectomy, and those on blood corticosterone level and adrenal ascorbic acid level were abolished by hypophysectomy. These results suggest that hypophysis-adrenal axis stimulation may play an important role in antiedematous effects of N-88 and HN-37.
1-(间三氟甲基苯基)-3-(2-羟乙基)-喹唑啉-2,4(1H,3H)-二酮[H-88]和1-(间三氟甲基苯基)-3-乙基吡啶并嘧啶-2,4(1H,3H)-二酮[HN-37]对大鼠角叉菜胶性爪肿胀的抗炎作用在肾上腺切除术后明显减弱或降低。因此，研究了这两种化合物对5-6周龄雄性Wistar大鼠垂体-肾上腺轴的影响。以100mg/kg的剂量口服H-88和10mg/kg的HN-37对完整动物产生相同程度的反应，即在峰值时间1小时时血皮质酮水平显著升高(360%)，3小时时肾上腺抗坏血酸水平降低(52-59%)，6-12小时时血糖水平升高(25-59%)，12-4小时时肝糖原水平升高(97-153%)。此外，在6-12小时时观察到垂体和肾上腺显著肥大(p<0.05)，在3-24小时时观察到胸腺和脾脏萎缩。HN-37对血皮质酮水平的作用约为H-88的10倍，对角叉菜胶性爪肿胀的作用也如此。两种化合物对血皮质酮水平的作用在肾上腺切除术后消失，对血皮质酮水平和肾上腺抗坏血酸水平的作用在垂体切除术后消除。这些结果表明，垂体-肾上腺轴刺激可能在H-88和HN-37的抗水肿作用中起重要作用。
