[Effects of quinazoline-2, 4(1H, 3H)-dione compound, H-88 and pyridopyrimidine-2, 4(1H, 3H)-dione compound, HN-37 on pituitary-adrenal axis in rats (author's transl)].
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.
D000311:Adrenal Glands / Q000378:metabolism; D000315:Adrenalectomy; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D007016:Hypophysectomy; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
D011744:Pyrimidinones; D011799:Quinazolines; C009027:H-88; C030801:HN-37; D001205:Ascorbic Acid; D003345:Corticosterone