The Synergistic Effect of Fluoxetine, Buspirone, and Sumatriptan with Sodium Valproate and Phenobarbitone in Experimental Models of Convulsion http://www.doi.org/10.26538/tjnpr/v7i4.24
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Epilepsy is one of the most common brain disorders, affecting at least 50 million persons worldwide. Antiepileptic’s have several dose-dependent side effects, necessitating a dose reduction or addition of an adjunct therapy. This study investigates the anticonvulsant activity of low dose phenobarbitone and sodium valproate when combined with buspirone, sumatriptan and fluoxetine. Mice were randomly divided into five groups; group I were treated with 0.2 ml of distilled water, group II were administered 20 mg/kg fluoxetine and 150 mg/kg sodium valproate, group III were administered 20 mg/kg sumatriptan and 150 mg/kg sodium valproate, group IV were administered 5 mg/kg buspirone and 150 mg/kg sodium valproate while group V were administered 150mg/kg of sodium valproate. One hour later, 70 mg/kg pentylenetetrazole (PTZ) was intraperitoneally administered to all mice. The onset of central nervous system (CNS) activity and percentage protection were recorded. The above was repeated using phenobarbitone (15 mg/kg). For strychnine (STN)-induced convulsion, the procedure was repeated with 1 mg/kg strychnine used in place of PTZ. For maximal electroshock shock -induced convulsion, mice were subjected to electroshock current of 50 mA for 0.2 seconds after one hour of administering the drugs as done in the other methods. Sumatriptan and sodium valproate combination significantly delayed the onset of CNS activity when compared with the negative control (p<0.05) in PTZ-induced convulsion. Fluoxetine and buspirone in combination with sodium valproate significantly delayed the onset of CNS activity (p<0.0001) against STN-induced convulsion. The different drugs in combination with phenobarbitone protected the mice against MES and PTZ-induced convulsion.
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World Health Organization (WHO). Epilepsy Fact Sheet. 2023. Available from: https://www.who.int/newsroom/fact-sheets/detail/. [Accessed on 27/03/2023].
Beghi E. The Epidemiology of Epilepsy. Neuroepidemiology 2020; 54:185-191.
Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children.Epileptic Disord.2015; 17(2):117–123.
GrzegorzewskaAM, Wiglusz MS, Landowski J, Cubała, WJ, Włodarczyk A, & Szarmach J. Multiple Comorbidity Profile of Psychiatric Disorders in Epilepsy. J. Clin. Med., 2021; 10(18), 4104.
Amelia JS, Louise S, Caroline H, and Milena G. Anxiety and depressive disorders in people with epilepsy:A metaanalysis. Epilepsia. 2017; 58(6):973–982, 201.
Perucca E, Beghi E, Dulac O, Shorvon S, Tomson T. Assessing risk to benefit ratio in antiepileptic drug therapy. Epilepsy Res. 2000; 41(2):107-39.
Fishman J, Kalilani L, Song Y, Swallow E, Wild I. Antiepileptic Drug Titration and Related Health Care Resource Use and Costs. J Manag Care Spec Pharm. 2018; 24(9):929-938.
Besag FMC. Approaches to reducing the incidence of lamotrigine-induced rash. CNS Drugs 2000; 13:21–23.
Bonnycastle D. D., Giarman N. J. and Paasonen M. K. Anticonvulsant compounds and 5-hydroxytryptamine in rat brain. Br. J. Pharmacol (1957); 12, 228–231.
Kilian M. and Frey HH. Central monoamines and convulsive thresholds in mice and rats. Neuropharmacology1973; 12:681–692.
Buterbaugh CG. Effects of drugs modifying central serotonergic function on the response of extensor and nonextensor rats to maximal electroshock.1978; Life Sci. 23:2393–2904.
Przegalinski E. Monoamines and the pathophysiology of seizure disorders, in Handbook of Experimental Pharmacology Frey, H. H. and Janz, D., eds), 1985; pp101–137.
Hiramatsu M K, Kawanaga K, Kabuto H and Mori A. Reduced uptake and release of 5-hydroxytryptamine and taurine in the cerebral cortex of epileptic El mice. Epilepsy Res. 1987; 1:40–44.
Dailey JW, Yan QS, Mishra PK, Burger RL, Jobe PC. Effects of fluoxetine on convulsions and on brain serotonin as detected by microanalysis in genetically epilepsy prone rats. J Pharmacol Exp Ther 1992; 2:533– 540
Gerber K, Filakovszky J, Halasz P and Bagdy G. The 5-HT1A agonist 8-OH-DPAT increases the number of spikewave discharges in a genetic rat model of absence epilepsy. Brain Res.1998; 807, 243–245
Filakovszky J, Gerber K and Bagdy G. A serotonin-1A receptor agonist and N-methyl-D-aspartate receptor antagonist oppose each other’s effects in a genetic rat epilepsy model. Neurosci. Lett 1999; 261:89–92
Lӧscher W. Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review. Meth. Find. Exp. Clin. Pharmacol. 1984; 6:531–547.
Prendiville S, Gale K. Anticonvulsant effect of fluoxetine on focally evoked limbic motor seizures in rats. Epilepsia, 1993; 34:381–384.
Yan QS, Jobe PC, Cheong JH, Ko KH and Dailey JW. Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy prone rats. Naunyn-Schmiedebergs Arch. Pharmacol. 1994; 350:149–152
Browning RA, Hoffman WE and Simonton RL. Changes in seizure susceptibility after intracerebral treatment with 5,7-dihydroxy-tryptamine: role of serotonergic neurones. Ann. N. Y. Acad. Sci. 1978; 305:437–456.
Statnick MA, Maring-Smith ML, Clough RW, Wang C, Dailey JW, Jobe PC and Browning RA. Effects of 5,7-dihydroxy-tryptamine on audiogenic seizures in genetically epilepsy prone rats. Life Sci.1996; 59:1763–1771.
Dailey JW, Reith ME, Yan QS, Li M Y and Jobe PC. Anticonvulsant doses of carbamazepine increase hippocampal extracellular serotonin in genetically epilepsyprone rats: dose–response relationships. Neurosci. Lett 1997; 227:13–16.
Ahmad S, Fowler LJ and Whitton PS. Lamotrigine, carbamazepine and phenytoin differentially alter extracellular levels of 5-hydroxytryptamine, dopamine and amino acids. Epilepsy Res.2005; 63:141–149.
NgoBum E, Schmutz M, Meyer C, Rakotonirina A, Bopelet M. Anticonvulsant properties of the methanolic extract of Cyperus articulates (Cyperaceae). J Ethnopharmacol.2001; 76:145-150.
Bolanle O.I, Oviasogie OD, Owolabi OJ, Akhigbemen AM, Obarisiagbon AP, Osaigbovo AC. Evaluation of the AntiConvulsant Activity of Aqueous Leaf Extract of Jatropha curcas (Euphorbiaceae) in Mice: Trop J. Nat Prod. Res,2018; 2(11):489–493.
Porter RJ, Cereghino JJ, Gladding GD. Antiepileptic drug development program. Cleve Clin1984; 51: 293-305
Humphrey P, Feniuk W, Marriott A, Tanner R, Jackson M, Tucker M. Preclinical studies on the anti-migraine drug, sumatriptan. European neurology 1991; 31:282- 290.
Johnson DE, Rollema H, Schmidt AW, McHarg AD. Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain. European journal of pharmacology2001; 425:203-210
White HS. Mechanisms of antiepileptic drugs. In: Porter R, Chadwick D, eds. Epilepsies II. Boston: ButterworthHeinemann, 1997; 1-30.
Kelly KM, Gross RA, Macdonald RL . Valproic acid selectively reduces the low-threshold (T) calcium in rat nodose neurons. Neurosci Lett 1990; 116: 233-238.
Rogawski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol Rev 1990; 42:223-286.
White SH. Comparative Anticonvulsant and Mechanistic Profile of the Established and Newer Antiepileptic Drugs. Epilepsia,1999; 4O (Suppl. 5):S2-S10.
Korpi ER, Grűnder G, Lűddens H. Drug interactions at GABA(A) receptors. Prog Neurobiol 2002; 67:113-159.
Madeja M, Stocker M, Mushoff V. Potassium current in epilepsy: effect of the epileptogenic agent pentylenetetrazole on a cloned potassium channel. Brain Research, 1994; 656:287-294.
Okada M., Kaneko S., Hirano T., Ishida M., Kondo T., Otani K. and Fukushima Y. Effects of zonisamide on extracellular levels of monoamine and its metabolite, and on Ca2+-dependent dopamine release. Epilepsy Res1992; 13:113–119
Dailey JW, Yan QS, Adams-Curtis LE, Ryu JR, Ko KH, Mishra PK and Jobe PC. Neurochemical correlates of antiepileptic drugs in the genetically epilepsy-prone rat (GEPR). Life Sci.1996; 58:259–266.
Peroutka SJ. 5-Hydroxytryptamine receptor subtypes: molecular, biochemical and physiological characterization. Trends in neurosciences, 1988; 11(11);496-500
Masand PS and Gupta S. Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry 1999; 7(2):69-84.
Bigler, E D. Neurophysiology, neuropharmacology and behavioral relationships of visual system evoked afterdischarges: A review. Neurosci Biobehav Rev 1977; 1(2), 95–112.
Browning RA, Nelson DK. Variation in threshold and pattern of electroshock-induced seizures in rats depending on site of stimulation. Life science 1985; 37(23): 2205-2211.
Kasthuri S. A review: animal models used in the screening of antiepileptic drugs neuropsy. Int. Res J of pharmaceutical and Appld Sci. (IRJPAS), 2013; 3(3):18-23.
Jana Vasković. Neurotransmitters. Available at ken https://www.kenhub.com/en/l ibrary/anatomy/neurotransmitters(2022).Accessed
Chau PL. New insights into the molecular mechanisms of general anaesthetics. Br J Pharmacol 2010; 161(2):288-307
Löscher W, Rogawski MA. How theories evolved concerning the mechanism of action of barbiturates. Epilepsia2012; 53 Suppl 8:12-25.
Martone CH, Nagelhout J, Wolf SM. Methohexital: a practical review for outpatient dental anesthesia. Anesth Prog.1991; 38(6):195-199.