RESEARCH PAPER
No effect of agmatine on the protective activity of clobazam and pregabalin against maximal electroshock-induced seizures in mice
1
Department of Pathophysiology, Medical University, Lublin, Poland
2
Isobolographic Analysis Laboratory, Institute of Agricultural Medicine, Lublin, Poland
3
Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland
Corresponding author
Jarogniew J. Łuszczki
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Department of Pathophysiology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2010;4(1):36-39
KEYWORDS
ABSTRACT
The aim of this study was to assess the influence of agmatine (AGM – an endogenous neuromodulator / neurotransmitter in the brain) on the protective action of two antiepileptic drugs (clobazam [CLB] and pregabalin [PGB]) in the mouse maximal electroshock seizure (MES) model. Results indicate that AGM at a dose of 100 mg/kg, i.p., 45 min before the test had no significant effect on the anticonvulsant action of CLB or PGB in the MES test in mice. Moreover, the examined combination of AGM with CLB and PGB (at doses from the MES test) did not affect motor coordination in the chimney test and muscular strength in the grip-strength test in mice, indicating no acute adverse effects in animals. Based on the results from this study, it can be concluded that the lack of effect of AGM on the anti-convulsant action of CLB and PGB in the mouse MES model associated with no acute adverse effects in animals, make the combinations of AGM with CLB and PGB neutral from a preclinical point of view.
REFERENCES (27)
1.
Raasch W, Schafer U, Chun J, Dominiak P: Biological signifi cance of agmatine, an endogenous ligand at imidazoline binding sites. Br J Pharmacol 2001, 133, 755–780.
2.
Arteni NS, Lavinsky D, Rodrigues AL, Frison VB, Netto CA: Agmatine facilitates memory of an inhibitory avoidance task in adult rats. Neurobiol Learn Mem 2002, 78, 465–469.
3.
Bence AK, Worthen DR, Stables JP, Crooks PA: An in vivo evaluation of the antiseizure activity and acute neurotoxicity of agmatine. Pharmacol Biochem Behav 2003, 74, 771–775.
4.
Demehri S, Homayoun H, Honar H, Riazi K, Vafaie K, Roushanzamir F, Dehpour AR: Agmatine exerts anticonvulsant eff ect in mice: modulation by alpha 2 adrenoceptors and nitric oxide. Neuropharmacology 2003, 45, 534–542.
5.
Gilad GM, Gilad VH: Accelerated functional recovery and neuroprotection by agmatine after spinal cord ischemia in rats. Neurosci Lett 2000, 296, 97–100.
6.
Lavinsky D, Arteni NS, Netto CA: Agmatine induces anxiolysis in the elevated plus maze task in adult rats. Behav Brain Res 2003, 141, 19–24.
7.
Olmos G, DeGregorio-Rocasolano N, Paz Regalado M, Gasull T, Assumpcio Boronat M, Trullas R, Villarroel A, Lerma J, Garcia-Sevilla JA: Protection by imidazol(ine) drugs and agmatine of glutamateinduced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor. Br J Pharmacol 1999, 127, 1317–1326.
8.
Su RB, Wei XL, Zheng JQ, Liu Y, Lu XQ, Li J: Anticonvulsive eff ect of agmatine in mice. Pharmacol Biochem Behav 2004, 77, 345–349.
9.
Zomkowski AD, Hammes L, Lin J, Calixto JB, Santos AR, Rodrigues AL: Agmatine produces antidepressant-like eff ects in two models of depression in mice. Neuroreport 2002, 13, 387–391.
10.
Reis DJ, Regunathan S: Is agmatine a novel neurotransmitter in brain? Trends Pharmacol Sci 2000, 21, 187–193.
11.
Luszczki JJ, Czernecki R, Wojtal K, Borowicz KK, Czuczwar SJ: Agmatine enhances the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock seizure model. J Neural Transm 2008, 115, 1485-1494.
12.
Loscher W, Fassbender CP, Nolting B: The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. II. Maximal electroshock seizure models. Epilepsy Res 1991, 8, 79–94.
13.
Taylor CP, Angelotti T, Fauman E: Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 2007, 73, 137-150.
14.
Sills GJ, Butler E, Thompson GG, Brodie MJ: Pharmacodynamic interaction studies with topiramate in the pentylenetetrazol and maximal electroshock seizure models. Seizure 2004, 3, 287–295.
15.
Piletz JE, May PJ, Wang G, Zhu H: Agmatine crosses the blood-brain barrier. Ann N Y Acad Sci 2003, 1009, 64–74.
16.
Litchfi eld JT, Wilcoxon F: A simplifi ed method of evaluating dose-eff ect experiments. J Pharmacol Exp Ther 1949, 96, 99–113.
17.
Luszczki JJ, Ratnaraj N, Patsalos PN, Czuczwar SJ: Isobolographic analysis of interactions between loreclezole and conventional antiepileptic drugs in the mouse maximal electroshock-induced seizure model. Naunyn-Schmiedeberg’s Arch Pharmacol 2006, 373, 169–181.
18.
Boissier JR, Tardy J, Diverres JC: Une nouvelle methode simple pour explorer l’action tranquilisante: le test de la cheminee. Med Exp (Basel) 1960, 3, 81–84
19.
Gonzalez C, Regunathan S, Reis DJ, Estrada C: Agmatine, an endogenous modulator of noradrenergic neurotransmission in the rat tail artery. Br J Pharmacol 1996, 119, 677–684.
20.
Yang XC, Reis DJ: Agmatine selectively blocks the N-methyl-Daspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther 1999, 288, 544–549.
21.
Weng XC, Gai XD, Zheng JQ, Li J: Agmatine blocked voltage-gated calcium channel in cultured rat hippocampal neurons. Acta Pharmacol Sin 2003, 24, 746–750.
22.
Morrissey JJ, Klahr S: Agmatine activation of nitric oxide synthase in endothelial cells. Proc Assoc Am Physicians 1997, 109, 51–57.
23.
Auguet M, Viossat I, Marin JG, Chabrier PE: Selective inhibition of inducible nitric oxide synthase by agmatine. Jpn J Pharmacol 1995, 69, 285–287.
24.
Demady DR, Jianmongkol S, Vuletich JL, Bender AT, Osawa Y: Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Mol Pharmacol 2001, 59, 24–29.
25.
Bian F, Li Z, Off ord J, Davis MD, McCormick J, Taylor CP, Walker LC: Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modifi ed mice. Brain Res 2006, 1075, 68-80.
26.
Micheva KD, Taylor CP, Smith SJ: Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons. Mol Pharmacol 2006, 70, 467-476.
27.
Brodie MJ, Schachter SC: Fast Facts. Epilepsy, 2nd edn., Health Press, Oxford, 2001.
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