Effects of Valproyl Urea on Neurons of The Cerebral Cortex and Cerebellar Purkinje Cells in Rats

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Onrawee Khongsombat
Chamnan Patarapanich
Mayuree H.Tantisira
Boonyong Tantisira


Preliminary studies in various animal models have established a greater anticonvulsant activity as well as broader margin of safety with less unwanted effects of N-(2-propylpentanoyl) urea (VPU) than its parent compound, valproic acid. We present herein the effects of VPU on neurons of the cerebral cortex and cerebellar Purkinje cells of anesthetized rats assessed by microiontophoretic technique and micropressure ejection. Similar to micropressure ejection of valproic acid, locally applied VPU depressed spontaneous firing of both neurons of the cerebral cortex and cerebellar Purkinje cells in a dose-dependent manner. Depressant effect on spontaneously firing Purkinje cells of VPU but not that of valproic acid was abolished in the presence of bicuculline given microiontophoretically. However, neither effect of VPU nor valproic acid was affected by strychnine. Further studies to probe interaction between VPU and other well established excitatory amino acid neurotransmitters of the brain given microiontophoretically were carried out on Purkinje cells. VPU exhibited different profile of responses from those of valproic acid which reversibly depressed excitant effect of glutamate and aspartate while had no effect on depressant effect evoked by either GABA or glycine. Virtually no effect of VPU was observed in corresponding environment. In conclusion, the present study demonstrated that VPU per se was able to exert anticonvulsant activity by different mechanisms than those exhibited by its parent compound, valproic acid. Interaction with GABAA receptor may at least, in part, involved in the anticonvulsant activity of VPU. More experiments are needed to identify other possible mechanisms of action of this compound.


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