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J Adv Res. 2014 Sep;5(5):587-94. doi: 10.1016/j.jare.2013.08.002. Epub 2013 Aug 22.

Enhanced efficacy and reduced side effects of diazepam by kava combination.

Journal of advanced research

Rasha A Tawfiq, Noha N Nassar, Wafaa I El-Eraky, Ezzeldein S El-Denshary

Affiliations

  1. Egyptian Patent Office, Academy of Scientific Research and Technology, 101 Kasr El-Eini St., Cairo, Egypt.
  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Eini St., Cairo, Egypt.
  3. Department of Pharmacology, National Research Center, El-Tahrir St., Giza, Egypt.

PMID: 25685527 PMCID: PMC4294317 DOI: 10.1016/j.jare.2013.08.002

Abstract

The long term use of antiepileptic drugs possesses many unwanted effects; thus, new safe combinations are urgently mandated. Hence, the present study aimed to investigate the anticonvulsant effect of kava alone or in combination with a synthetic anticonvulsant drug, diazepam (DZ). To this end, female Wistar rats were divided into two subsets, each comprising 6 groups as follows: group (i) received 1% Tween 80 p.o. and served as control, while groups (ii) and (iii) received kava at two dose levels (100 and 200 mg/kg, p.o.). The remaining three groups received (iv) DZ alone (10 mg/kg p.o.) or kava in combination with DZ (v) (5 mg/kg, p.o.) or (vi) (10 mg/kg, p.o.). Results of the present study revealed that kava increased the maximal electroshock seizure threshold (MEST) and enhanced the anticonvulsant effect of diazepam following both acute and chronic treatment. Moreover, neither kava nor its combination with DZ impaired motor co-ordination either acutely or chronically. Furthermore, kava ameliorated both the reduction in locomotor activity as well as changes in liver function tests induced by chronic administration of DZ. Moreover, no elevation was shown in the creatinine concentration vs. control group following chronic administration of kava or DZ either alone or in combination with kava. In conclusion, the present study suggests the possibility of combining a low dose DZ with kava to reduce harmful effects and might be recommended for clinical use in patients chronically treated with this synthetic anticonvulsant drug.

Keywords: AED, antiepileptic drug; ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; Anticonvulsant; BDZ, benzodiazepine; DZ, diazepam; Diazepam; ECT, electroconvulsive treatment; FDA, Food and Drug Administration; GABA, γ-aminobutyric acid; GABAA, γ-aminobutyric acid type A; Kava; Locomotor activity; MEST; MEST, maximal electroshock threshold; OTC, over the counter; WHO, World Health Organization

References

  1. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13;33(8):1372-89 - PubMed
  2. Psychopharmacology (Berl). 2003 Oct;170(1):33-41 - PubMed
  3. CNS Drugs. 2002;16(11):731-43 - PubMed
  4. Clin Pharmacol Ther. 2005 May;77(5):415-26 - PubMed
  5. Neuropharmacology. 2008 Aug;55(2):148-53 - PubMed
  6. Bull Exp Biol Med. 2009 Jun;147(6):719-21 - PubMed
  7. Epilepsy Res. 1991 Mar;8(2):79-94 - PubMed
  8. Brain Res. 2008 Dec 30;1246:29-40 - PubMed
  9. Psychopharmacology (Berl). 1994 Dec;116(4):469-74 - PubMed
  10. Life Sci. 2002 Apr 19;70(22):2581-97 - PubMed
  11. Epilepsy Res. 2002 Jun;50(1-2):67-70 - PubMed
  12. Enzyme. 1971;12(5):561-73 - PubMed
  13. Neuropharmacology. 2009 Jun;56(8):1124-30 - PubMed
  14. Neuropharmacology. 2006 Feb;50(2):133-42 - PubMed
  15. Curr Top Med Chem. 2005;5(1):69-85 - PubMed
  16. J Neural Transm. 1983;56(2-3):127-38 - PubMed
  17. J Pharmacol Toxicol Methods. 2008 Sep-Oct;58(2):129-46 - PubMed
  18. Pharmacol Ther. 2001 Apr;90(1):21-34 - PubMed
  19. Eur J Neurol. 2006 May;13(5):445-50 - PubMed
  20. Planta Med. 2003 Jun;69(6):496-9 - PubMed
  21. Phytomedicine. 2007 Sep;14(9):605-12 - PubMed
  22. Am J Clin Pathol. 1957 Jul;28(1):56-63 - PubMed
  23. Res Commun Chem Pathol Pharmacol. 1993 Jul;81(1):68-76 - PubMed
  24. Basic Clin Pharmacol Toxicol. 2005 Nov;97(5):289-95 - PubMed
  25. Curr Opin Pharmacol. 2005 Feb;5(1):47-52 - PubMed
  26. J Endocrinol Invest. 1995 Dec;18(11):853-6 - PubMed
  27. J Pharmacol Exp Ther. 2000 Sep;294(3):909-15 - PubMed
  28. Natl Toxicol Program Tech Rep Ser. 2012 Mar;(571):1-186 - PubMed
  29. Phytochemistry. 2003 Oct;64(3):673-9 - PubMed

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