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Pentilentetrazol ile Sıçanlarda Oluşturulan Deneysel Epilepsi Modelinde Oksolamin Sitratın antikonvulsan Etkisi

Year 2020, Volume: 11 Issue: 1, 92 - 99, 03.03.2020

Abstract

Amaç: Dünya çapında milyonlarca kişi epilepsi hastası olarak sorun yaşamaktadır ve hastaların %25'inde şu anda mevcut bulunan antiepileptik ilaçlara karşı dirençli nöbetler gözlenmektedir. Bu nedenlerle, etkili ve henüz tolere edilebilen daha fazla sayıda antiepileptik ilaca ihtiyaç duyulmaya devam etmektedir. Oksolamin sitrat, pre-klinik verilere dayanarak antiepileptik aktiviteye sahip olabilen yaygın bir antitussif ilaçtır.

Materyal-Metot: Sıçanlar randomize bir şekilde intraperitoneal (i.p.) Oksolamin ile iki farklı dozda ve plasebo şeklinde tedavi edildi ve daha sonrasında güçlü bir nöbet indükleyici bileşik olan pentilentetrazole (PTZ) i.p. olarak maruz bırakıldı. Oksolaminin epilepsi için sıçan modelimizde antiepileptik özelliklere sahip olup olmadığını belirlemede sıçanların hemen sonrasındaki nöbet aktivitesi elektroensefalografi (EEG), Racine'nin konvülsiyon ölçeği (RCS) ve ilk miyoklonik jerk (TFMJ) zamanı ile değerlendirildi.

Bulgular: Plasebo ile karşılaştırıldığında, her iki dozda Oksolamin, nöbet aktivitesini önemli ölçüde inhibe etti. Ortalama EEG spike dalga yüzdesi % 75.3'ten (plasebo) % 35.8'e (düşük doz, p <0.01) ve %28.6'ya (yüksek doz, p <0.0001) azaldı. RCS, ortalama 5.7'den (plasebo) 4.7'ye (düşük doz, p <0.001) ve 3.3'e (yüksek doz, p <0.0001) düştü. TFMJ ortalama 62.5s'den (plasebo), 177.5s'ye (düşük doz, p <0.001) ve 223.3s'ye (yüksek doz, p <0.0001) yükseldi.

Sonuç: Yaygın bir antitussif ilaç olan Oksolamin sitrat, PTZ ile indüklenen status epileptikus sıçan modelinde nöbet aktivitesini baskılamaktadır. Refrakter epilepsi için devam eden etkili yeni tedaviler bulma gereksinimi göz önüne alındığında, oksolaminin antiepileptik olarak kullanılma olasılığı daha ileri düzeyde araştırılmalıdır.

References

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  • Motamedi, G., Meador, K., 2003. Epilepsy and cognition. Epilepsy Behav. 4 (Suppl. 2), S25–38.
  • Schmidt, D., 2009. Drug treatment of epilepsy: options and limitations. Epilepsy Behav. 15, 56–65.
  • Eddy, C.M., Rickards, H.E., Cavanna, A.E., 2011. The cognitive impact of antiepileptic drugs. Ther. Adv. Neurol. Disord. 4, 385–407.
  • Kanner, A.M., et al., 2012. Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence. Epilepsy Behav. 24, 156–168.
  • Chang, B.S., Lowenstein, D.H., 2003. Epilepsy. N. Engl. J. Med. 349, 1257–1266.
  • Cowan, L.D., 2002. The epidemiology of the epilepsies in children. Ment. Retard. Dev. Disabil. Res. Rev. 8, 171–181.
  • Reddy, D.S., Kuruba, R., 2013. Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int. J. Mol. Sci. 14, 18284–18318.
  • Shin, E.-J., et al., 2011. Role of oxidative stress in epileptic seizures. Neurochem. Int. 59, 122–137.
  • Hancock, J.T., Desikan, R., Neill, S.J., 2001. Role of reactive oxygen species in cell signaling pathways. Biochem. Soc. Trans. 29, 345–350.
  • Elger, C.E., Helmstaedter, C., Kurthen, M., 2004. Chronic epilepsy and cognition. Lancet Neurol. 3, 663–672.
  • Curia, G., et al., 2014. Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic? Curr. Med. Chem. 21, 663–688.
  • Kang, J.-Q., Macdonald, R.L., 2009. Making sense of nonsense GABA(A) receptor mutations associated with genetic epilepsies. Trends Mol. Med. 15, 430–438.
  • Olsen, R.W., DeLorey, T.M., Gordey, M., Kang, M.H., 1999. GABA receptor function and epilepsy. Adv. Neurol. 79, 499–510.
  • McNamara, J.O., Huang, Y.Z., Leonard, A.S., 2006. Molecular signaling mechanisms underlying epileptogenesis. Sci. STKE re12 (2006).
  • Nalivaiko, E., Michaud, J.C., Soubrié, P., Le Fur, G., Feltz, P., 1997. Tachykinin neurokinin-1 and neurokinin-3 receptor-mediated responses in guinea-pig substantia nigra: an in vitro electrophysiological study. Neuroscience 78, 745–757.
  • Liu, H., Mazarati, A.M., Katsumori, H., Sankar, R., Wasterlain, C.G., 1999. Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc. Natl. Acad. Sci. U. S. A. 96, 5286–5291.
  • Penix, L.P., Thompson, K.W., Wasterlain, C.G., 1996. Selective vulnerability to perforant path stimulation: role of NMDA and non-NMDA receptors. Epilepsy Res. Suppl. 12, 63–73.
  • Silvestrini B, Pozzatti C. Pharmacological properties of 3-phenyl-5β diethylaminoethyl-1, 2, 4-oxadiazole. Br J Pharmacol Chemother 1961; 16: 209-217.
  • Erbaş, O., Solmaz, V., Aksoy, D., 2015. Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures. Neurol. Res. 37, 1096–1101.
  • Kubin, L., Alheid, G.F., Zuperku, E.J., McCrimmon, D.R., 2006. Central pathways of pulmonary and lower airway vagal afferents. J. Appl. Physiol. 101, 618–627.
  • Aeby, A., Poznanski, N., Verheulpen, D., Wetzburger, C., Van Bogaert, P., 2005. Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases. Epilepsia 46, 1937–1942.
  • Fernández, I.S., et al., 2012. Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep. Epilepsia 53, 1185–1195.
  • Lüttjohann, A., Fabene, P.F., van Luijtelaar, G., 2009. A revised Racine’s scale for PTZ-induced seizures in rats. Physiol. Behav. 98, 579–586.
  • Canning, B.J., 2007. Encoding of the cough reflex. Pulm. Pharmacol. Ther. 20, 396–401.
  • Walker, B.R., Easton, A., Gale, K., 1999. Regulation of limbic motor seizures by GABA and glutamate transmission in nucleus tractus solitarius. Epilepsia 40, 1051–1057.
  • Epilepsy. World Health Organization. Erişim linki: http://www.who.int/news-room/factsheets/detail/epilepsy. (Erişim tarihi: 10 Aralık 2019).
  • Avoli, M., et al., 2002. Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro. Prog. Neurobiol. 68, 167–207.
  • Mantegazza, M., Curia, G., Biagini, G., Ragsdale, D.S., Avoli, M., 2010. Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 9, 413–424.
  • Badawy, R.A.B., Harvey, A.S., Macdonell, R.A.L., 2009. Cortical hyperexcitability and epileptogenesis: understanding the mechanisms of epilepsy - part 1. J. Clin. Neurosci. 16, 355–365.
  • Werner, F.-M., Coveñas, R., 2011. Classical neurotransmitters and neuropeptides involved in generalized epilepsy: a focus on antiepileptic drugs. Curr. Med. Chem. 18, 4933–4948.
  • Meldrum, B.S., 1995. Neurotransmission in epilepsy. Epilepsia 36 (Suppl. 1), S30–35.
  • Bolser, D.C., Poliacek, I., Jakus, J., Fuller, D.D., Davenport, P.W., 2006. Neurogenesis of cough, other airway defensive behaviors and breathing: A holarchical system? Respir. Physiol. Neurobiol. 152, 255–265.
  • Polverino, M., et al., 2012. Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip. Respir. Med. 7, 5.
  • Canning, B.J., Mori, N., 2011. Encoding of the cough reflex in anesthetized guinea pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R369–377.
  • Coleridge, J.C., Coleridge, H.M., 1984. Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev. Physiol. Biochem. Pharmacol. 99, 1–110.
  • Shannon, R., Baekey, D.M., Morris, K.F., Lindsey, B.G., 1998. Ventrolateral medullary respiratory network and a model of cough motor pattern generation. J. Appl. Physiol. 84, 2020–2035.
  • Shannon, R., Baekey, D.M., Morris, K.F., Li, Z., Lindsey, B.G., 2000. Functional connectivity among ventrolateral medullary respiratory neurones and responses during fictive cough in the cat. J. Physiol. (Lond.) 525 (Pt 1), 207–224.
  • Canning, B.J., et al., 2014. Anatomy and neurophysiology of cough: CHEST Guideline and Expert Panel report. Chest 146, 1633–1648.
  • Jhamandas, J.H., Harris, K.H., 1992. Excitatory amino acids may mediate nucleus tractus solitarius input to rat parabrachial neurons. Am. J. Physiol. 263, R324–330.
  • Rutecki, P., 1990. Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 31 (Suppl 2), S1–6.
  • Havaldar FH, Patil AR (2009) Synthesis of biologically active 3-[4-(4-substituted amino-4-yl-methyl-5-thione[1,3,4]-oxadiazole-2-yl-methoxy)-phenyl]-2-phenyl-3H-quinazolin-4-ones. Asian J Chem 21:5267–5272.
  • Mehta DK, Das R, Dua K (2009) Synthesis, antimicrobial and anti-inflammatory activity of some new 1,3,4-oxadiazoles and 1,3,4-oxadiazole-2-thione derivatives as mannich bases containing furan moiety. Int J Chem Sci 7:225–234.
  • Nagalakshmi G (2008) Synthesis, antimicrobial and anti-inflammatory activity of 2,5-disubstituted-1,3,4-oxadiazoles. Indian J Pharm Sci 70:49–55.
  • Husaini A, Ahmad FJ, Ajmal M, Ahuja P (2008) Synthesis of 1-(4-phenoxyphenyl)-3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]propan-1-ones as safer anti-inflammatory and analgesic agents. J Serb Chem Soc 73:781–791.
  • George S, Parameswaran MK, Chakraborty AR, Ravi TK (2008) Synthesis and evaluation of the biological activities of some 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-one derivatives. Acta Pharm 58:119–129.
  • Mishra AR, Singh DV, Mishra RM (2005) Synthesis and antifungal activity of new 1,3,4-oxadiazolo[3,2-b]-s-triazine-5-ones and their thiones analogues. Indian J Heterocycl Chem 14:289–292.
  • Girges MM (1994) Synthesis and pharmacological evaluation of novel series of sulfonate ester-containing 1,3,4-oxadiazole derivatives with anticipated hypoglycemic activity. Arzneimittelforschung 44:490–495.
  • Revanasiddappa BC, Subrahmanyam EVS (2009) Chloramine-T mediated synthesis of 1,3,4-oxadiazoles. Orient J Chem 25:707–710.
  • Maslat AO, Abussaud M, Tashtoush H, Al-Taalib M (2002) Synthesis, antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives. Pol J Pharmacol 54:55–59.
  • Borg, S., Luthman, K., Nyberg, F., Terenius, L., & Hacksell, U. (1993). 1, 2, 4-Oxadiazole derivatives of phenylalanine: potential inhibitors of substance P endopeptidase. European journal of medicinal chemistry, 28(10), 801-810.
  • Lankau, H. J., Unverferth, K., Grunwald, C., Hartenhauer, H., Heinecke, K., Bernöster, K., ... & Rundfeldt, C. (2007). New GABA-modulating 1, 2, 4-oxadiazole derivatives and their anticonvulsant activity. European journal of medicinal chemistry, 42(6), 873-879.
  • S.J. Gilani, O. Alam, S.A. Khan, N. Siddiqui, H. Kumar, Der Pharmacia Lettre, 2009, 1, 1-8.
  • A. Zarghi, S. Hamedi, F. Tootooni, B. Amini, B. Sharifi, M. Faizi, S.A. Tabatabai, A. Shafiee, Sci Pharm., 2008, 76, 185–201.
Year 2020, Volume: 11 Issue: 1, 92 - 99, 03.03.2020

Abstract

References

  • Wyllie, E., 2015. Wyllie’s Treatment of Epilepsy: Principles and Practice, sixth edition. Wolters Kluwer Health.
  • Motamedi, G., Meador, K., 2003. Epilepsy and cognition. Epilepsy Behav. 4 (Suppl. 2), S25–38.
  • Schmidt, D., 2009. Drug treatment of epilepsy: options and limitations. Epilepsy Behav. 15, 56–65.
  • Eddy, C.M., Rickards, H.E., Cavanna, A.E., 2011. The cognitive impact of antiepileptic drugs. Ther. Adv. Neurol. Disord. 4, 385–407.
  • Kanner, A.M., et al., 2012. Depression and epilepsy: epidemiologic and neurobiologic perspectives that may explain their high comorbid occurrence. Epilepsy Behav. 24, 156–168.
  • Chang, B.S., Lowenstein, D.H., 2003. Epilepsy. N. Engl. J. Med. 349, 1257–1266.
  • Cowan, L.D., 2002. The epidemiology of the epilepsies in children. Ment. Retard. Dev. Disabil. Res. Rev. 8, 171–181.
  • Reddy, D.S., Kuruba, R., 2013. Experimental models of status epilepticus and neuronal injury for evaluation of therapeutic interventions. Int. J. Mol. Sci. 14, 18284–18318.
  • Shin, E.-J., et al., 2011. Role of oxidative stress in epileptic seizures. Neurochem. Int. 59, 122–137.
  • Hancock, J.T., Desikan, R., Neill, S.J., 2001. Role of reactive oxygen species in cell signaling pathways. Biochem. Soc. Trans. 29, 345–350.
  • Elger, C.E., Helmstaedter, C., Kurthen, M., 2004. Chronic epilepsy and cognition. Lancet Neurol. 3, 663–672.
  • Curia, G., et al., 2014. Pathophysiogenesis of mesial temporal lobe epilepsy: is prevention of damage antiepileptogenic? Curr. Med. Chem. 21, 663–688.
  • Kang, J.-Q., Macdonald, R.L., 2009. Making sense of nonsense GABA(A) receptor mutations associated with genetic epilepsies. Trends Mol. Med. 15, 430–438.
  • Olsen, R.W., DeLorey, T.M., Gordey, M., Kang, M.H., 1999. GABA receptor function and epilepsy. Adv. Neurol. 79, 499–510.
  • McNamara, J.O., Huang, Y.Z., Leonard, A.S., 2006. Molecular signaling mechanisms underlying epileptogenesis. Sci. STKE re12 (2006).
  • Nalivaiko, E., Michaud, J.C., Soubrié, P., Le Fur, G., Feltz, P., 1997. Tachykinin neurokinin-1 and neurokinin-3 receptor-mediated responses in guinea-pig substantia nigra: an in vitro electrophysiological study. Neuroscience 78, 745–757.
  • Liu, H., Mazarati, A.M., Katsumori, H., Sankar, R., Wasterlain, C.G., 1999. Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc. Natl. Acad. Sci. U. S. A. 96, 5286–5291.
  • Penix, L.P., Thompson, K.W., Wasterlain, C.G., 1996. Selective vulnerability to perforant path stimulation: role of NMDA and non-NMDA receptors. Epilepsy Res. Suppl. 12, 63–73.
  • Silvestrini B, Pozzatti C. Pharmacological properties of 3-phenyl-5β diethylaminoethyl-1, 2, 4-oxadiazole. Br J Pharmacol Chemother 1961; 16: 209-217.
  • Erbaş, O., Solmaz, V., Aksoy, D., 2015. Inhibitor effect of dexketoprofen in rat model of pentylenetetrazol-induced seizures. Neurol. Res. 37, 1096–1101.
  • Kubin, L., Alheid, G.F., Zuperku, E.J., McCrimmon, D.R., 2006. Central pathways of pulmonary and lower airway vagal afferents. J. Appl. Physiol. 101, 618–627.
  • Aeby, A., Poznanski, N., Verheulpen, D., Wetzburger, C., Van Bogaert, P., 2005. Levetiracetam efficacy in epileptic syndromes with continuous spikes and waves during slow sleep: experience in 12 cases. Epilepsia 46, 1937–1942.
  • Fernández, I.S., et al., 2012. Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep. Epilepsia 53, 1185–1195.
  • Lüttjohann, A., Fabene, P.F., van Luijtelaar, G., 2009. A revised Racine’s scale for PTZ-induced seizures in rats. Physiol. Behav. 98, 579–586.
  • Canning, B.J., 2007. Encoding of the cough reflex. Pulm. Pharmacol. Ther. 20, 396–401.
  • Walker, B.R., Easton, A., Gale, K., 1999. Regulation of limbic motor seizures by GABA and glutamate transmission in nucleus tractus solitarius. Epilepsia 40, 1051–1057.
  • Epilepsy. World Health Organization. Erişim linki: http://www.who.int/news-room/factsheets/detail/epilepsy. (Erişim tarihi: 10 Aralık 2019).
  • Avoli, M., et al., 2002. Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro. Prog. Neurobiol. 68, 167–207.
  • Mantegazza, M., Curia, G., Biagini, G., Ragsdale, D.S., Avoli, M., 2010. Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 9, 413–424.
  • Badawy, R.A.B., Harvey, A.S., Macdonell, R.A.L., 2009. Cortical hyperexcitability and epileptogenesis: understanding the mechanisms of epilepsy - part 1. J. Clin. Neurosci. 16, 355–365.
  • Werner, F.-M., Coveñas, R., 2011. Classical neurotransmitters and neuropeptides involved in generalized epilepsy: a focus on antiepileptic drugs. Curr. Med. Chem. 18, 4933–4948.
  • Meldrum, B.S., 1995. Neurotransmission in epilepsy. Epilepsia 36 (Suppl. 1), S30–35.
  • Bolser, D.C., Poliacek, I., Jakus, J., Fuller, D.D., Davenport, P.W., 2006. Neurogenesis of cough, other airway defensive behaviors and breathing: A holarchical system? Respir. Physiol. Neurobiol. 152, 255–265.
  • Polverino, M., et al., 2012. Anatomy and neuro-pathophysiology of the cough reflex arc. Multidiscip. Respir. Med. 7, 5.
  • Canning, B.J., Mori, N., 2011. Encoding of the cough reflex in anesthetized guinea pigs. Am. J. Physiol. Regul. Integr. Comp. Physiol. 300, R369–377.
  • Coleridge, J.C., Coleridge, H.M., 1984. Afferent vagal C fibre innervation of the lungs and airways and its functional significance. Rev. Physiol. Biochem. Pharmacol. 99, 1–110.
  • Shannon, R., Baekey, D.M., Morris, K.F., Lindsey, B.G., 1998. Ventrolateral medullary respiratory network and a model of cough motor pattern generation. J. Appl. Physiol. 84, 2020–2035.
  • Shannon, R., Baekey, D.M., Morris, K.F., Li, Z., Lindsey, B.G., 2000. Functional connectivity among ventrolateral medullary respiratory neurones and responses during fictive cough in the cat. J. Physiol. (Lond.) 525 (Pt 1), 207–224.
  • Canning, B.J., et al., 2014. Anatomy and neurophysiology of cough: CHEST Guideline and Expert Panel report. Chest 146, 1633–1648.
  • Jhamandas, J.H., Harris, K.H., 1992. Excitatory amino acids may mediate nucleus tractus solitarius input to rat parabrachial neurons. Am. J. Physiol. 263, R324–330.
  • Rutecki, P., 1990. Anatomical, physiological, and theoretical basis for the antiepileptic effect of vagus nerve stimulation. Epilepsia 31 (Suppl 2), S1–6.
  • Havaldar FH, Patil AR (2009) Synthesis of biologically active 3-[4-(4-substituted amino-4-yl-methyl-5-thione[1,3,4]-oxadiazole-2-yl-methoxy)-phenyl]-2-phenyl-3H-quinazolin-4-ones. Asian J Chem 21:5267–5272.
  • Mehta DK, Das R, Dua K (2009) Synthesis, antimicrobial and anti-inflammatory activity of some new 1,3,4-oxadiazoles and 1,3,4-oxadiazole-2-thione derivatives as mannich bases containing furan moiety. Int J Chem Sci 7:225–234.
  • Nagalakshmi G (2008) Synthesis, antimicrobial and anti-inflammatory activity of 2,5-disubstituted-1,3,4-oxadiazoles. Indian J Pharm Sci 70:49–55.
  • Husaini A, Ahmad FJ, Ajmal M, Ahuja P (2008) Synthesis of 1-(4-phenoxyphenyl)-3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]propan-1-ones as safer anti-inflammatory and analgesic agents. J Serb Chem Soc 73:781–791.
  • George S, Parameswaran MK, Chakraborty AR, Ravi TK (2008) Synthesis and evaluation of the biological activities of some 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-one derivatives. Acta Pharm 58:119–129.
  • Mishra AR, Singh DV, Mishra RM (2005) Synthesis and antifungal activity of new 1,3,4-oxadiazolo[3,2-b]-s-triazine-5-ones and their thiones analogues. Indian J Heterocycl Chem 14:289–292.
  • Girges MM (1994) Synthesis and pharmacological evaluation of novel series of sulfonate ester-containing 1,3,4-oxadiazole derivatives with anticipated hypoglycemic activity. Arzneimittelforschung 44:490–495.
  • Revanasiddappa BC, Subrahmanyam EVS (2009) Chloramine-T mediated synthesis of 1,3,4-oxadiazoles. Orient J Chem 25:707–710.
  • Maslat AO, Abussaud M, Tashtoush H, Al-Taalib M (2002) Synthesis, antibacterial, antifungal and genotoxic activity of bis-1,3,4-oxadiazole derivatives. Pol J Pharmacol 54:55–59.
  • Borg, S., Luthman, K., Nyberg, F., Terenius, L., & Hacksell, U. (1993). 1, 2, 4-Oxadiazole derivatives of phenylalanine: potential inhibitors of substance P endopeptidase. European journal of medicinal chemistry, 28(10), 801-810.
  • Lankau, H. J., Unverferth, K., Grunwald, C., Hartenhauer, H., Heinecke, K., Bernöster, K., ... & Rundfeldt, C. (2007). New GABA-modulating 1, 2, 4-oxadiazole derivatives and their anticonvulsant activity. European journal of medicinal chemistry, 42(6), 873-879.
  • S.J. Gilani, O. Alam, S.A. Khan, N. Siddiqui, H. Kumar, Der Pharmacia Lettre, 2009, 1, 1-8.
  • A. Zarghi, S. Hamedi, F. Tootooni, B. Amini, B. Sharifi, M. Faizi, S.A. Tabatabai, A. Shafiee, Sci Pharm., 2008, 76, 185–201.
There are 54 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Original Article
Authors

Mümin Alper Erdoğan 0000-0003-0048-444X

Oytun Erbaş 0000-0002-2515-2946

Publication Date March 3, 2020
Submission Date December 23, 2019
Published in Issue Year 2020 Volume: 11 Issue: 1

Cite

Vancouver Erdoğan MA, Erbaş O. Pentilentetrazol ile Sıçanlarda Oluşturulan Deneysel Epilepsi Modelinde Oksolamin Sitratın antikonvulsan Etkisi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi. 2020;11(1):92-9.

SDÜ Sağlık Bilimleri Dergisi, makalenin gönderilmesi ve yayınlanması dahil olmak üzere hiçbir aşamada herhangi bir ücret talep etmemektedir. Dergimiz, bilimsel araştırmaları okuyucuya ücretsiz sunmanın bilginin küresel paylaşımını artıracağı ilkesini benimseyerek, içeriğine anında açık erişim sağlamaktadır.