Antipyretic Action of Isatin and Its Analogues in Mice and Rats

The effects of isatin (2,3-dioxo-indole) and isatin analogues (5-methylisatin, 6-hydroxyisatin, 7-ethylisatin, N-acety- lisatin) were tested on prostaglandin E2 (PGE2)-induced fever in mice and rats. Two modes of administration were tested. Isatin or an analogue was injected simultaneously with PGE2 and the development of fever was tested, or the test compound was given 30 min following PGE2 administration and the effects on the already existing fever were measured, in mice and in rats. Isatin in a dose of 3.12 mg/kg ip was found to block the development of PGE2-induced fever in mice, while in a dose of 12.5 mg/kg ip it attenuated the existing fever. In rats isatin in a dose of 12.5 mg/kg ip blocked fever initiation, and at 25.0 mg/kg ip attenuated existing PGE2-induced fever. In mice, 5-methylisatin in a dose of 0.21 mg/kg ip blocked the initiation of fever, and at 6.72 mg/kg ip attenuated the existing fever. In rats in a dose of 3.36 mg/kg ip it blocked the development of fever, and at 13.44 mg/kg ip attenuated existing PGE2-induced fever. In mice 5,6-dimetylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and attenuated the existing fever in mice, in rats in a dose of 0.42 mg/kg ip it blocked the initiation of fever, and at 0.21 mg/kg ip attenuated the existing PGE2-induced fever. In mice 6-hydroxyisatin in a dose of 5.2 mg/kg blocked the development of fever, and at 10.4 mg/kg attenuated the existing fever. In rats in a dose of 10.40 mg/kg ip it blocked fever development and also attenuated the existing fever. In mice, 7-ethylisatin in a dose of 0.02 mg/kg ip both blocked fever initiation and also attenuated the existing fever. In rats, a dose of 0.11 mg/kg both blocked fever initiation and also attenuated the existing fever. In mice, N-acethylisatin in the dose of 0.005 mg/kg blocked fever initiation, while at 1.024 mg/kg it attenuated existing fever, in rats, in a dose of 0.096 mg/kg it blocked fever initiation, and at 0.384 mg/kg attenuated the existing fever. The results demonstrate that 7-ethyl- and N-acetylisatin are the most effective of these compounds both in blocking the development of PGE2-induced fever and also in attenuating existing the PGE 2-induced fever.