4-Ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone(M73101)の薬理学的研究

Abstract

The anti-inflammatory activity and the mode of action of M73101, a new non-steroid analgesic anti-inflammatory agent, were investigated in experimental animals and compared with those of reference drugs. M73101 inhibited the increase in vascular permeability induced by acetic acid and its activity was more potent than that of phenylbutazone. M73101 showed a marked inhibitory effect against rat paw edema induced by various phlogistic agents (carrageenin, dextran, histamine, serotonin and bradykinin) and the activities were equal to or more potent than those of aminopyrine, mepirizole and tiaramide HCl. M73101 also inhibited the edema induced by mustard, scalding and anti-rat rabbit serum in rats. In addition, the anti-edematous effect of M73101 on carrageenin-induced rat paw edema was not influenced by spinalectomy or adrenalectomy, indicating that the anti-inflammatory action of M73101 was not mediated by the central nervous system and the adrenals. Local and oral administration of M73101 inhibited significantly the leucocyte migration into the fluid of CMC pouch in rats and the activity was more potent than phenylbutazone, suggesting that the anti-inflammatory effect of M73101 was due to the direct action at the inflamed site. On the other hand, M73101 did not show any marked activities on the experimental chronic inflammatory models. From these results, it is suggested that M73101 may be useful for clinical application as a basic analgesic, anti-inflammatory drug with remarkable anti-inflammatory activity in acute and subacute cases. The mechanism of the anti-inflammatory action of M73101 probably involves inhibition of an increase in vascular permeability and leucocyte migration.