JRI 

Forouzan Rahmani Corresponding Author
- Department of Anatomy, Faculty of Medicine, Shahr-e-Kord University of Medical Sciences, Shahr-e-Kord, Iran
Masoumeh Delaram
- Department of Midwifery, Faculty of Nursing & Midwifery, Shahrekord University of Medical Science & Health Services, Shahr-e-Kord, Iran
Nasrin Forouzandeh
- Department of Psychological Nursing, Faculty of Nursing & Midwifery, Shahrekord University of Medical Science & Health Services, Shahr-e-Kord, Iran

Received: 4/1/2006 Accepted: 4/1/2006 - Publisher : Avicenna Research Institute

Related Articles

 

Other Format

 


Abstract

Introduction: One of the most important complications of antiepileptic drugs (AEDs) is increased congenital malformations. The risk of malformations in such fetuses is 7-10% compared to 2-4% in the general population. Lamotrigine is a recently introduced AED, with fewer teratogenic effects than that of the older ones and without reported teratogenic effects in most cases. Recently some malformations have been reported related to Lamotrigine use in human beings but the reports are scanty and contradictory and no particular patterns of malformations have been presented. This study has been done to detect the teratogenic effects of this drug in mouse fetus. Materials & Methods: In this study, NRMI mice were divided into four groups: I) control group 1, II) control group 2, with intraperitoneal administration of ethanol solution, III) case group 1, with intraperitoneal administration of three 25 mg/kg doses of Lamotrigine and IV) case group 2, with intraperitoneal administration of three 75 mg/kg doses of Lamotrigine. Injections were made during the 9th to the 18th days of gestation. On the 18th day of gestation, the fetuses were harvested. The body weight and height were measured and malformations in vertebral column, limbs and cranium were looked for and recorded. Malformations were compared in the four groups by SPSS software. Results: In the groups with 25 & 75 mg/kg Lamotrigine administrations, reduction of body weight and height and increased malformations of vertebral column and limbs were noticeable in a dose dependent fashion compared to the control groups number 1 & 2_ cranial malformations were insignificant. Conclusion: Based on the results, Lamotrigine can be considered as a risk factor for the increase of malformations in the treated animals. As a number of researchers believe that decrease of serum folate and methionine are effective in the appearance of malformations and they may implicate the situation, further studies on the mechanisms of Lamotrigine from this point of view are recom-mended.


Keywords: Lamotrigine, Mouse, Fetus, Teratogenic, Epilepsy, Pregnancy, Anticoagulant drugs, Folic acid


To cite this article:


References

  1. بهادري مسلم، شكور عباس. نقايص زمان تولد. رويان شناسي پزشكي لانگمن. تجديد نظر هشتم. انتشارات چهر،1380، صفحات: 128-127.
  2. Bastaki S.A.M., Padmanabhan R., Abdulrazzaq Y.M., Chandranth S.I., Shafiulla M. Studies on the terato-genic effect of lamotrigine in mouse fetuse. Frontier in fetal health (a Global perspective). Volume 3, Number 11/12, 2001,295 2001;3(11-12):295.
  3. Beghi E., Annegers J.F., Pergnancy registries in epilep-sy. Epilepsia.2001;42(11):1422-5.
  4. Mark S., Yerby M.S., Kaplan P., Tran T. Risks and management of pregnancy in women with epilepsy. Cleveland clinic Journal of Medicine.2004;71(2suppl): 25-37.
  5. Richens A. Safety of Lamotrigine. Epilepsia.1994;35 (Suppl 5):37-40.
  6. Curry W.J., Kulllling D.L. Newer Anticonvulsant drugs; gabapentin, lamotrigine, febamate, tiagbin, fos-phentyoin. Am Fam Physician.1998;57:513-520.
  7. Young L.T., Robb J.C., Patelis- Siotis I., et al. Acute treatment of bipolar depression with gabapentine. Biol Psychiatery.1997;42:851-53.
  8. Kusumakar V., Yathman Ln. Lamotrigine Treatment of rapid cycling bipolar disorder. Am J Psychiatery.1997; 154:1171-2.
  9. Mather G.G., Levy R.H. Anticonvulsant. Levy R.H., Thummel K.E., Tager W.F., Hanster P.D., Eichelbaum M. Metabolic Drug interactions, Philadelphia:Lippicott Williams & Wilkiins Company Kluwer.2000;218-219.
  10. James O., Mc Nammara. Druge effective in the thera-py of the epilepsia. Hardman J., Limbird Lee E., Good-man & Gillmans the pharmacological basis of thera-peutic. 10th Edition Mc Grow hill Company.2001;539-540.
  11. Ohman I., Vitols S., Tomson T. Lamotrigine in preg-nancy: pharmacokinetics during delivery, in the neo-nate, and during lactation.Epilepsia.2000;41(6):709-13.
  12. Rambeck B., Kurlemann G., Stodieck S.R., May T. W., Jurgens U. Concentrations of Lamotrigine in a mother on lamotrigine treatment and her new born child. Eur J Clin pharmacol.1997;51(6):481-4.
  13. Tomson T., Ohman I., Vitols S. Lamotrigine in preg-nancy and Latction: a case report. Epilepsia.1997;38 (9):1039-40.
  14. Leppik I.E., Antiepileptic drugs in development: pros-pects for the near future. Epilepsia.1994;35(suppl 4): 29-40.
  15. Iqbal M.M., Ryan W.G., Effect of antimanic mood-stabilizing drugs on fetuses, Neonates,and Nursing Infants. Sourthern Medical journal.2001;94(3):304-22.
  16. Loiuseau P., New medical treatment of epilepsy. Presse- Med.1996;23;25(10):481-3.
  17. Marchi N.S., Azouble R., Tognola W.A. Teratogenice effects of lomotrigine on rat fetal brain: amorpho-metrice study. Arq Neuropsiquiatr.2001;59(2-B):362-4.
  18. Morrell M.J. The new antiepileptic drugs and woman: efficacy, reproductive health, pregnancy and fetal out-come. Epilepsia.1996;37(suppl 6):34-44.
  19. Cunnigton M., Tennis P. Lamotrigine and a risk of malformation in pregnancy. Neurology online.2005;64: 955-960.
  20. Fazio A., Artesi C., Russo M., Trio R., Oterio G., Pisani F. A liquid chromatographic assay using a high-speed colmn for the determination of lamotrigine a new antiepileptic drugin human plasma. Ther Drug Monti. 1992;14(6): 509-12
  21. Devinsky O., Vazquez B., Luciano D. New antiepi-leptic drugs for children: felbamate, gabapentin, lamot-rigine, and vigabatrin : J Child Neural.1994;9(Suppl 1 S):33-45.
  22. Canavero S., Bonicalzi V. Drug therapy of trigeminal neuralgia.2006;6(3):429-40.
  23. Lampl C., Katsarava Z., Diener H.C., Limmroth V. Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. J Neurol Neurosurg Psychiatry.2005;76(12):1730-2.
  24. Nahlik L. Lamotrigine (lamictal) when monoteraphy just isn’t enough. The university of Chicago Hospital. 1996;l37:5-6.
  25. Haddad J., Messer J. Feta lalcohol syndrom. Report of three siblings. Neuropediatrics.1994;25:109-11.
  26. Jacobson J.L., Jacobson S.W. Sokol R.J. Mmmartier S.S., at al. Teratogenice effect of alcohol on infant development. Alcohol Clin Exp Res.1993;17:174-83.
  27. Gage J.J.C., Sulik K.K. Pathogenesis of athanol-induced hydronrphrosis and hydroureter as demonst-rated following in vivo expousre of mouse embryo. Teratology.1991;44:299-312.
  28. Maurceri H.J., Lee W.H., Coneay S. Effects of etha-nol on insuline-like growth factor-II relase from fetal organssss. Alcohol Clin Exp Res.1994;18:35-41.
  29. Padmanabhan R., Abdulrazzaq Y.M., Bastaki S.M., Shafiulla M., Chandra S.I. Experimental studies on reproductive toxicologic effects of lamotrigine in mice. Birth Defects Res Part B Dev Repord Toxicol.2003;68 (5):428-38.
  30. Nau H. Pharmacokinetices of valproic acid and its metabolites in pregnant patient. In: Janz D (ed). Epi-lepsy, pregnancy and the child: from Raven press. New York: USA,131-44,1981.
  31. Nulman I., Laslo D., Koren G. Treatment of epilepsy in pregnancy. Drugs.1999;57:535-544.
  32. Minns R.A. Folic acid and neural tube defects. Spinl cord1998;34:460-465.
  33. Perucca E. Birth defects after prenatal exposure to antiepileptic drugs. Lancent Neural.2005 ;4(11):781-6

COPE
SID
NLM
AJMB
IJBMLE
IJBMLE

Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.