Thermoregulatory and In-vivo Anti-inflammatory Effects of Vigabatrin In Rat and Mice

Abstract

Effects of acute administration of vigabatrin (VGB) that has significant GABA-mimetic properties were studied for its antiinflammatory, antigranuloma effects in rats and thermoregulatory actions in mice. Treatment of rats with VGB (125, 250 and 500 mg/kg, i.p doses) caused a significant and persistent inhibition in the carrageenan induced paw edema. Inhibitory effect at high dose (500 mg/kg, which was about 10-fold of the maximal effective dose 50 mg/kg in humans) was 40-, 41- and 39% of the control at 2-, 3- and 4 hours afier the treatment. In cotton-pellet-granuloma study, only the high dose was significantly (P<0.05) effective and inhibition in granuloma was 17 and 28% of the control at 250 and 500 mg/kg doses, respectively. In another model, leukocyte migration to the inflamed peritoneal cavity was used as a parameter in rats. In this model, VGB (500 mg/kg, i.p) induced a significant (P<0.05) reduction in leukocyte migration to the inflamed peritoneal cavity when administered 30 min before carrageenan. This was comparable to indomethacin (10 mg/kg) that also caused a significant (P<0.05) reduction in leukocyte migration. The inhibition in the leukocyte migration was 66 and 61% with VGB and indomethacin, respectively. In thermoregulation studies, the rectal temperature of normothermic mice declined dose dependently. In another part of this study all the doses of VGB induced a significant reduction in body temperature at 45 min following drug administration in yeast-induced hyperpyrexic mice. The hypothermic response diminished after 90 min, 3 hours and 6 hours of treatment at 125, 250 and 500 mg/kg doses respectively and none of the dose showed any change in rectal temperature at 24-hour study point. The results of the present study indicate that vigabatrin has the potential to induce anti-edema, antigranuloma and leukocyte anti-migratory effects in inflamed peritoneal cavity and reduce the rectal temperature in normothermic as well as hyperthermia-induced mice with acute regimen. These effects are thought to be the result of GABA accumulation, its interaction with PG biosynthesis and other neuromediators.