鎮痛, 解熱および抗炎症作用におけるAminopyrineとPhenopyrazoneとの配合効果

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Combined effect of aminopyrine with phenopyrazone (1,4-diphenyl-3,5-pyrazolidinedione) at the weight ratio of 1 : 1 on analgesic, antipyretic and anti-inflammatory activities was examined by oral administration in experimental animals. ED_<50> values (mg/kg) of aminopyrine, phenopyrazone, and the combination were 117.2 (n=85), more than 640,and 126.2 (n=85), respectively, for suppressing the phenylquinone-induced writhing in mice, 13.6 (n=56), more than 640,and 10.2 (n=56), respectively, for reducing the yeast-induced fever in rats, and 182.3 (n=128), 574.0 (n=47), and 216.4 (n=78), respectively, for inhibiting the carrageenin-induced edema in rats. Their LD_<50> values in mice were 522.6 (n=110), more than 3200,and 848.5 (n=110) mg/kg, p.o., respectively. Anti-writhing activity of aminopyrine in the mice pretreated with phenopyrazone daily for 5 days was significantly better than that in the mice pretreated with a vehicle 24 hr after the last administration, and the plasma level of phenopyrazone at the time was almost nil. The anti-writhing activity of aminopyrine (60 mg/kg) was significantly potentiated by the addition of 60 mg/kg of phenopyrazone but not with 6 mg/kg. The parallel shift of the dose-response curve for aminopyrine to the left was significant by the addition of a fixed dose (60 mg/kg) of phenopyrazone to each dose of aminopyrine. These results suggest that analgesic and antipyretic activities of aminopyrine were potentiated by the combined use with phenopyrazone at the weight ratio of 1 : 1 without any potentiating effect on acute lethal toxicity, though the anti-inflammatory activity tended to be potentiated, and the synergism between the drugs appeared to be due to the raised sensitivity of the acting site.
公益社団法人日本薬学会の論文
1978-06-25

鎮痛, 解熱および抗炎症作用におけるAminopyrineとPhenopyrazoneとの配合効果

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