一新鎮痛剤としての2-Phenyl-4-dimethylaminopropylamino-6-ethoxy-3 (2H) pyridazinone hydrochloride (TM-3)の薬理学的研究

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From an analgesic screening test of 2-phenyl-3 (2H) pyridazinone derivatives, synthesized by Takahashi et al., 2-phenyl-4-dimetylaminopropylamino-6-ethoxy-3 (2H) pyridazinone hydrochloride (TM-3) was discovered to have pronounced analgesic activity. In the present paper, the pharmacological effects, particularly analgesic and anti-inflammatory effects of TM-3, are compared with those of aminopyrine (AP) or phenylbutazone (PB). 1) In an analgesic test using modified Haffners method on mice, the potency of TM-3 was approx. 6 times that of AP. 2) The analgesic effect of TM-3 tested by electric stimulation, hot plate and acetic acid stretching methods was equal to or more potent than that of AP. 3) TM-3 showed an inhibitory effect similar to that of PB on carrageenin, yeast and dextran-indued edema of rat paws. 4) In dermal tissue permeability tests of rats, TM-3 exhibited an equal or more potent inhibition as compared to PB. 5) In Winters cotton pellet granuloma test, TM-3 tended to inhibit granulation. 6) TM-3 showed an antipyretic effect comparable to that of AP on T. T. G. -induced rabbit fiver. 7) TM-3 exhibited an uricosuric effect on uric acid or adenine-induced hyperuricemic rats. 8) TM-3 did not exhibit anti-convulsive, muscle-relaxant or hypnotic effects and influenced slightly spontaneous respiration, blood pressure, EEG and isolated auricular movement of rabbits. 9) The acute and subacute toxicities of TM-3 were lower than that of AP and the safety margin of TM-3 as an analgesic agent was considerably higher than that of AP.
社団法人日本薬理学会の論文

一新鎮痛剤としての2-Phenyl-4-dimethylaminopropylamino-6-ethoxy-3 (2H) pyridazinone hydrochloride (TM-3)の薬理学的研究

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