Gabapentin and sodium valproate: a comparative study

ABSTRACT

Gabapentin [GBP], a new antiepileptic drug with proven efficacy in the control of partial epilepsy, and is suggested to be a more favorable alternate to sodium valproate [SVP] in the control of generalized epileptic seizures as it has less side effects and a more favorable pharmacokinetic properties. In view of the gama aminobutyric acid [GABA] enhancing properties of GBP and SVP and the documented involvement of GABA in the control of cognitive functions, it is theoretically suggested that both drugs may affect the cognitive functions. To compare the anticonvulsant activity of SVP and GBP and compare the effects of both drugs on motor coordination and cognitive functions. The anticonvulsant effects of serial intraperitoneal [IP] doses of SVP and GBP were compared in mice using the maximal electroshock stimulation [MES] and subcutaneous pentylenetetrazole [scPTZ] stimulation tests. The effects of serial IP doses of SVP and GBP on motor coordination were compared in mice using the righting reflex and the rotarod tests. The effects of single IP injection and of chronic oral administration of SVP, GBP or both were compared in rats using the passive avoidance test. Both SVP and GBP produced significant anticonvulsant activity in the MES test but the median effective dose [ED50], as calculated by Litchefield and Wilcoxon, of SVP [115 mg/kg] was significantly lower than ED50 of GBP [140 mg/kg]. SVP produced significant anticonvulsant activity in the scPTZ test [ED50 110 mg/kg] while GBP didn't produce a significant effect. SVP produced significantly more impairment of motor performance in the righting and rotarod tests. The median toxic dose was [TD50] of SVP was 350 mg/kg, and for GBP was 750 mg/kg. SVP produced significant inhibition of learning and memory retention after acute and chronic administration. On the other hand, GBP didn't produce any observable effect on learning or memory. GBP is likely to be clinical effective as a single agent therapy in generalized tonic clonic convulsions but not in generalized absence seizures. GBP is less likely than SVP to cause impairment of motor coordination and cognitive functions