Antinociceptive activity of vigabatrin in mice

ABSTRACT

Vigabatrin [an inhibitor of GABA catabolism] was examined for its antinociceptive activity, changes in locomotor activity and body temperature in mice after acute treatment over a period of 24 hours. Vigabatrin [125 and 500 mg/kg i.p] resulted in rapid antinociception within 15 min. At the low dose of vigabatrin this effect returned to normal after-45 min but persisted more than 12 hours at the high dose. With the same dose regimen, the locomotor activity declined significant, with persistence up to 24 hour of the treatment. The effect of this treatment on body temperature was dose related being significantly reduced at 15 min. It returned to normal after 6 hours of treatment with vigabatrin 500 mg/kg. Treatment with bicuculline [a specific GABA A-receptor antagonist] was found to be minimally effective to avert locomotor or body] temperature changes induced by vigabatrin. Picrotoxin [a GABA Aand GABA gated-chloride ion channel blocker] was also ineffective on the hot-plate latency, locomotion or body temperature. However, picrotoxin slightly though significantly [p<0.05] reversed the changes in locomotion and rectal temperature only at first observation [15 min]. On the other hand, naloxone did not antagonize the effect of vigabatrin on body temperature but caused a significant decline in hot-plate latency at 45 min, perhaps because of hepotentiation of naloxone by vigabatrin in the induction of hyperalgesic response. These effects are thought to be a result of neuromediator interactions with the probable involvement of GABA receptor mediated processes and a possible direct effect of drug