Effects of Coadministration of Vitamin C and Lamotrigine on some Pharmacological Properties of Lamotrigine in Laboratory Animals
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Abstract
Despite the continued development and release of new antiepileptic drugs, many patients have seizures that do not respond to drug therapy or have related side effects that preclude continued use. The present study is aimed at establishing the possible potentiation actions of vitamin C on the anticonvulsant effects of lamotrigine in acute and chronic seizure models and on the possible prevention and/or reversal of haematological side effects of lamotrigine.
This aim was achieved using maximal electroshock test (MEST)-induced seizure model for which the method of Swinyard and Kupferberg, (1985) was adopted, pentylenetetrazole-induced kindling model for which method described by Gupta et al., (2001) was employed and haematological analysis in which haemoglobin concentration, packed cell volume, red blood cell count, white blood cell count / differentials and platelets count were carried out. Lamotrigine and Vitamin C combination at doses of 50 mg/kg, 100 mg/kg and 400 mg/kg provided 16.67%, 50%, and 66.67% protection respectively against MEST-induced seizures. There was no significant (p < 0.05) difference in the mean recovery period. Lamotrigine only showed 0% protection against MEST-induced seizures. In PTZ induced kindling, Vitamin C (50 mg/kg and 400 mg/kg) showed a significant (p < 0.05) reduction (from 5.00 to 0.88 and 5.00 to 2.13 respectively) in the severity of seizure induced by sub-convulsive dose (35 mg/kg) of PTZ as compared to control group on day ten. Administration of lamotrigine caused a reduction in mean neutrophils count as against untreated control group. Addition of vitamin C (50 mg/kg and 100 mg/kg) to lamotrigine treated group caused an increase in neutrophils compared to lamotrigine only treated group. The results showed that vitamin C enhances the anticonvulsant and some haematological sideeffects of lamotrigine, thus may serve as an adjunct in treatment of epilepsy using lamotrigine.
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References
Armijo, J.A., Cuevas, A.L., Adin, J., (2000). Ion channels and epilepsy. Span. J. Neurol. 1, 25-41.
Baker, G.A., Jacoby, A. and Buck, D. (1997). Quality in life in people with epilepsy: a European study. Epilepsia, 38(3), 353-362.
Bazyan, A.S., Zhulin, V.V., Karpova, M.N., Klishina, N.Y., Glebov, R.N., (2001). Long-term reduction of benzodiazepine receptor density in the rat cerebellum by acute seizures and kindling and its recovery 6months later by a pentylenetetrazole challenge. Brain Res. 888, 212-220.
Cocito, L., Maffini, M., Loeb, C. (1994). Long-term observations on the clinical use of Lamotrigine as add-on drug in patients with Epilepsy. Epilepsy Res. 19:123-127. [PubMed].
Damiani, J.T., Christensen, R.C. (2000). Lamotrigine-associated neutropenia in a geriatric patient. Am J. Geriatr Psychiatry, 8:346. [PubMed].
De Camargo, O.A. and Bode, H. (1999). Agranulocytosis associated with Lamotrigine. British Medical Journal. 318:1179.
Edyta, S. and Stanislaw, J.C. (2014): Vitamin C: A New Auxiliary Treatment for Epilepsy?Pharmacological Reports (ELSEVIER) 66: 529-533.
Fadul, C.E., Meyer, L.P. and Jobst, B.C.et al. (2002). Agranulocytosis associated with Lamotrigine in a patient with low grade glioma. Epilepsia. 43:199-200 [PubMed].
Fernandez-Galan, M., Martin-Nunez, G. and Castellanos, F. et al. (2000) Lamotrigine-induced Agranulocytosis. Med Clin (Barc). 115:759 [pubmed].
Flanagan, R.J., and Dunk, L., (2008). Haematological toxicity of drugs used in psychiatry. Human Psychopharmacol. Clin. Experience 23:27-41.
Gonza ´ lez-Ram? ´rez, M., Razo-Jua ´ rez, L.I., Sauer-Ram? ´rez, J.L., Gonza ´ lez-Trujano, M.E., Salgado-Ceballos, H., Orozco-Suarez, S. (2010). Anticonvulsive effect of vitamin C on pentylenetetrazol-induced seizures in immature rats. PharmacolBiochemBehav; 97:267–72.
Gupta, Y.K., Shirma, M., Chaudhary, G., 2001. Antiepileptic activity of Panax Ginseng against Pentylenetetrazole-induced kindling in rats. Indian J. Pharmacol. 45(4), 502-506.
Keen, R. and Appleton R.E. (2006). Alternative Approaches to Conventional Antiepileptic Drugs in The Management of Paediatric Epilepsy. Archives of Diseases in Childhood, 91(11): 936-941.
Kellie, L., Leslie, P., Maureen, H., Amanda, M., Kingston, O., (2005). Lamotrigine induced neutropenia (case report). Canadian Journal of Psychiatry, Canadian Pychiatric Association. 50(4):242. [PubMed].
Lambert, O., Veyrac, G., Armand, C., Bourlon, S., Bourin, M., Jolliet, P. (2002). Lamotrigine induced neutropenia following two attemps to increase doses above 50mg/day with recovery between episodes. Adverse Drug React. Toxicol Rev. 21:157-159. [PubMed].
Le Drew, K., Philllips, L., and Hogan, M.et al. (2005). Lamotrigine-induced neutropenia. Can J. Psychiatry 50:242. [PubMed].
Loscher, W. and Schmidt, D. (2006). New horizons in the development of antiepileptic drugs: Innovative strategies. Epilepsy research, 69, 183-272.
Norman, C., Hummel, B. and Scharer, L.O.et al. (2002). Lamotrigine as adjunct to paroxetine in acute depression: a placebo controlled, double blind study. J. Clin. Psychiatry. 63:337-344. [PubMed].
Piyush, D., Sriram, R., Monica, A., Irina, S., Teril, G., (2007). Lamotrigine-induced neutropenia in a woman with schizoaffective disorder. Prim care companion. J Clin Psychiatry; 9(6): 471-472.
Porter, R. J. and Meldrum, B. S. (2004). Antiseizure Drugs. In:Basic and Clinical Pharmacology. McGraw Hill. (Ed). Katzung, G. B. 9th Edition, Pp. 379.
Rang, H.P., Dale, M.M., Ritter, J.M. and Morre, P.K. (2007). Pharmacology. 6th edition. Churchill Livingstone, Elsevier science limited, pp. 471, 575-584.
Ranganathan, L.N., Ramaratnam, S. (2009). Vitamins for epilepsy. The Cochrane Library.4:1-31.
Riazi, K., Roshanpour, M., Rafiei-Tabatabaei, N., Homayoun, H., Ebrahimi, F., Dehpour, A.R.(2006). The proconvulsant effect of sildenafil in mice: role of nitric oxide–Cgmp pathway. Br. J. Pharmacol, 147, 935-943.
Rivara, M., Patel, M.K., Zuliani, V. (2012). Inhibition of NaV1.6 Sodium channel currents by a novel series of 1,4-di-substituted-triazole derivatives obtained via copper-catalyzed click chemistry. Bio-org. Med. Chem. 22, 6401-6404.
Santos, I.M., Tome ´ Ada, R, Saldanha, G.B., Ferreira, P.M., Milita ˜o, G.C., Freitas, R.M. (2009). Oxidative stress in the hippocampus during experimental seizures can be ameliorated with the antioxidant ascorbic acid. Oxid Med Cell Longev;2:214–21.
Santos, L.F., Freitas, R.L., Xavier, S.M., Saldanha, G.B., Freitas, R.M. (2008) Neuroprotective actions of vitamin C related to decreased lipid peroxidation and increased catalase activity in adult rats after pilocarpine-induced seizures. PharmacolBiochem. Behav;89:1–5.
Sasa, M. (2006). A new frontier in Epilepsy: Novel Antiepileptogenic Drugs, Journal of Pharmacological Sciences, 100, 487-494.
Scheuer, M.L. (1996). Antiepileptic drugs. In current Neurologic drugs. Rowland, L.P., Klein, D.F. (Eds.) Brunner/Mazel, New York.
Schneider, O.M., Fla ´via, F.A., Freire-Royes, L.F., Rechia, F.M., de CarvalhoMyskiw, J., Gindri, F.N., et al. (2004). Ascorbate modulatespentylenetetrazol-induced convulsions biphasically. Neuroscience; 128:721–8.
Sepkuty, J.P., Kaplan, P.W. (2004). Haematological disorders. Available at http://professionals.epi.com/wi/print_section.ph? Section=haematologic. Accessed on 12/12/2017, 8:45am.
Sharon, P. (2013). Vitamin C Defeciency and Aneamia. LIVESTRONG.COM, Avilable at www.livestrong.com/article/353558-vitamin-c-defeciency-aneamia/ retrieved February 07, 2016.
Solvason, H.B. (2000). Agranulocytosis associated with lamotrigine. Am J. Psychiatry. 157:1704 [PubMed].
Sultana, R., Perluigi, M., Allan-Butterfield, D. (2013). Lipid peroxidation triggers neurodegeneration: a redox proteomics view in to the Alzheimer disease brain. Free Radic Boil Med; 65:1-14.
Swinyard, E.A. and Kupferberg, H.J. (1985). Antiepileptic drugs: detection, quantification and evaluation. Fed Proc, 44: 39-43.
Tome ´ Ada, R., Feitosa, C.M., Freitas, R.M. (2010). Neuronal damage and memory deficits after seizures are reversed by ascorbic acid? ArqNeuropsiquiatr; 68:579–85.
William, J.C., and David, L.K. (1998). Newer Antiepileptic Drugs: Gabapentin, Lamotrigine, Felbamate, Topiramate and Fosohenyton. Am Fam. Physician; 1:57(3): 513-520.
Young, N.S., (1994). Agranulocytosis (conference). J. Am. Med. Assoc. 271(12): 935-938.