Z47 Anti-inflammatory, Immune And Analgesic Effects And Mechanism

STUDIES ON THE ANTI-INFLAMMATORY -IMMUNE AND ANALGESIC EFFECTS AND THEIR MECHANISMS OF Z47 CAl LI (PHARMACOLOGY) WANG MINWEI ABSTRACT Z47 is a novel compound of Pyrrolizinones. It has been initially demonstrated that Z47 has a remarkable anti-inflammatory and analgesic activities with low toxicity, and has no injury to gastric mucosa. The anti-inflammatory-immune and analgesic effects and their mechanisms of Z47 were further investigated in this paper. In anti-inflammatory experiments, the ear edema induced by xylene and the increase in vascular permeability induced by acetic acid in mice were significantly inhibited by Z47 100-400mg/kg ( ig, same below). The hind paw edema induced by fresh egg white, His, 5-HT and heat, the inflammatory exudates and the leucocyto migratory reaction induced by carrageenan in rats were distinctly abated by Z47, and these effects were better than or similar with those of ibuprofen. It also showed the suppressive action to the proliferation of granuloma of rats induced by cotton-pellet in rats, was weaker than that of ibuprofen. In analgesic experiments, 25-200mg/kg of Z47 showed strong periphery analgesic action. It has been proved that Z47 provided analgesia better than or similar with ibuprofen in writhing induced by acetic and the second phase pain response induced by formaldehyde in mice. However, similar with ibuprofen, Z47 was less effective than morphine in the first phase pain response induced by formaldehyde. The central analgesic effects were exhibited by Z47 at the dose of 200-400mg/kg. It was far more effective than ibuprofen and indomethacin in the hot-plate and tail-flick test in mice, and naloxorie had no significant effect on its central analgesia. In immunological experiments, 50-200mg/kg of Z47 daily adiministration over 5-7d showed a visible inmmunosuppression effect. It decreased the carbon clearance rate of charcoal particles, inhibited the production of the hemolysin 3 immunized with SRBC and suppressed the delayed type hypersensitivity reaction induced by DNCB in mice. But these effects were obviously weaker than that of cyclophosphamidum. Meanwhile, it had no significant effect on the index of thymus and spleen. In addition, 200mg/kg of Z47 markedly inhibited PCA reaction of rats. Its effect was similar with that of chlorpheniramine. It was found that Z47 inhibited the production or release of NO, but promoted the production or release of histamine, and had no effect on the production or release of PGE, MDA and 5-HT; it showed non-competitive inhibition to contraction of the isolated guinea pig ileum induced by histamine, 5-HT and Ca2~ ( PD2 4.43, 5.37 and 3.88, respectively); it also promoted the function of HPAA and increased the stability of red cell membranes in studying of mechanisms. These results indicated that Z47 may be a promising novel NSAID with strong analgesic activity. Its mechanism is complicated and different from that of conventional NSAIDs.