Effects of N(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in spontaneous recurrent seizure rats

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Background: N(2-propylpentanoyl) urea (VPU) is a new valproic acid (VPA) analog with higher anticonvulsant activity than its parent compound in various animal models including seizure acutely induced by pilocarpine. Objective: Investigate its effects on hippocampal amino acid neurotransmitters in spontaneous recurrent seizure (SRS) rats. Methods: Pilocarpine hydrochloride was used to induce status epilepticus (SE). Animals were visually observed for two hours/day for an episode of SRS for six weeks. Microdialysis experiment was performed to detect hippocampal amino acid neurotransmitters on those rats that developed SRS. Results: In comparison to normal rats, hippocampal glutamate, gamma-aminobutyric acid (GABA), and glycine, significantly increased in SRS rats. Occurrence of SRS in the faces of increased level of inhibitory neurotransmitters suggests the key role played by glutamate in the genesis and control of SRS. Based on the observation in pilocarpine-induced SE, the level of glutamate in SRS rats significantly decreased by a clinically effective anticonvulsant, VPA (300 and 600 mg/kg, i.p). Similar profile on hippocampal glutamate was also exhibited by VPU (50 and 100 mg/kg, i.p.). Conclusion: The possible role of VPU in controlling seizure in SRS rats and subsequently human temporal lobe epilepsy as VPA was suggested.

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  • 1. Turski L Ikonomidou C Turski WA Bortolotto ZA Cavalheiro EA. Cholinergic mechanism and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. Synapse. 1989; 3:154-71.

  • 2. Cavalheiro EA Leite JP Bortolotto ZA Turski WA Ikonomidou C Turski L. Long term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneously recurrent seizures. Epilepsia. 1991; 32: 778-82.

  • 3. Mathern GW Babb TL Leite JP Pretorious K Yeoman KM Kuhlman PA. The pathogenic and progressive features of chronic human hippocampal epilepsy. Epilepsy Res. 1996; 26:151-61.

  • 4. Turski WA Valheiro EA Coimbra C da Penha Berzaghi M Ikonomidou C Turski L. Only certain antiepileptic drugs prevent seizures induced by pilocarpine. Brain Res. 1987; 434:281-305.

  • 5. Leite JP Cavalheiro EA. Effects of conventional antiepileptic drugs in a model of spontaneous recurrent seizure in rats. Epilepsy Res. 1995; 20:93-104.

  • 6. Klitgaard H Matagne A Gobert J Wulfert E. Evidence for a unique profile of levetiracetam in rodent models of seizures and epilepsy. Eur. J. Pharmacol. 1998; 353: 191-206.

  • 7. Glien M Brandt C Potschka H Loscher W. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizurs in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia. 2002; 43: 350-7.

  • 8. Cavalheiro EA. The pilocarpine model of epilepsy. Ital J Neuro Sci. 1995; 16: 33-7.

  • 9. Sarkisian MR. Overview of the current animal models for human seizure and epileptic disorders. Epilepsy Behav. 2001; 2:201-16.

  • 10. Leite JP Garcia-Cairasco N Cavalheiro EA. New insight from the use of pilocarpine and kainate model. Epilepsy Res. 2002; 50: 93-103.

  • 11. Majores M Elis J Wiestler OD Becker AJ. Molecular profiling of temporal lobe epilepsy: comparison of data from human tissue samples and animal models. Epilepsy Res. 2004; 60: 173-8.

  • 12. Saisorn B Patarapanich C Janwitayanuchit W. Synthesis of monouric analogues of valproic acid. Thai J Pharm Sci. 1992; 16:145-50.

  • 13. Tantisira B Tantisira MH Patarapanich C Sooksawate T Chunngam T. Preliminary evaluation of the anticonvulsant activity of a valproic acid analog: N- (2-propylpentanoyl)urea. Res Commun Mol Pathol Pharmacol. 1997; 97:151-64.

  • 14. Khongsombat O Watanabe H Tantisira B Patarapanich C Tantisira MH. Acute effects of N-(2- propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats. Epilepsy Res. 2008; 79:151-7.

  • 15. Racine RJ. Modification of seizure activity by electrical stimulation: II. Motor Seizures. Electroencephalogr. Clin. Neurophysiol. 1972; 32: 295-9.

  • 16. Turski WA Cavalheiro EA Schwarz M Czuczwar S Kleinrok Z Turski L. Limbic seizures produced by pilocarpine in rats: behavioral electroencephalographic and neuropathological study. Behav Brain Res. 1983; 9:315-35.

  • 17. Paxinos G Watson C. The Rat brain in stereotaxic coordinaes 2nd ed. San Diago:Academic Press 1986.

  • 18. Lindroth P Mopper K. High performance liquid chromatographic determination of subpicromole derivatization of amino acids by precolumn fluorescence derivatization o-phthaldialdehyde. Anal Chem. 1979; 51:1667-74.

  • 19. Szyndler S Wierzba-Bobrowicz T Skorzewska A Maciejak P Walkowiak J Lechowicz W et al. Behavioral biochemical and histological studies in a model of pilocarpine-induced spontaneous recurrent seizure. Pharmacol Biochem Behav. 2005; 81:15-23.

  • 20. Smith M Wilcox KS White S. Discovery of antiepileptic drugs. Neurotherap. 2007; 4:12-17.

  • 21. Cavalheiro EA Fernandes MJ Turski L Naffah- Mazzacoratti MG. Spontaneous recurrent seizures in rats: amino acid and monoamine determination in the hippocampus. Epilepsia. 1994; 35:1-11.

  • 22. Klitgaard H Matagne A Grimee R Vanneste-Goemaere J Margineanu D. Electrophysiological neurochemical and regional effects of levetiracetam in the rat pilocarpine model of temporal lobe epilepsy. Seizure. 2003; 12: 92-100.

  • 23. Thomas PM Phillips JP O’Connor WT. Microdialysis of lateral and medial temporal lobe during temporal lobe epilepsy surgery. Surg Neurol. 2005; 63: 70-9.

  • 24. During MJ Spencer DD. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet. 1993; 342:1607-10.

  • 25. Wilson CL Maidment NT Shomer MH Behnke EJ Ackerson L I Fried I et al. Comparison of seizure related amino acid release in human epileptic brain versus a chronic kainite rat model of hippocampal epilepsy. Epilepsy Res. 1996; 26: 245-54.

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