Effect of artesunate on maximal electroshock and pentylenetetrazole-induced seizures in albino mice

Sanjana K., Shyamjith M., Deepa B., Sathynarayana N. Rao, Preethi G. Pai


Artemisinin-based combination therapies are highly efficacious, and they are now listed as first-line therapies for uncomplicated
malaria in most countries where malaria is endemic. Neurotoxicity of artemisinins is a growing concern. However, no studies have reported its antiepileptic or epileptogenesis potential, hence the present study was undertaken to explore the activity of artesunate in experimentally induced seizures in rodent models. Artesunate at doses 36.4 and 72.8 mg/kg respectively significantly reduced the duration of the hind limb extensions (3.033±1.493 and 2.033±1.383, respectively) when compared to the control (P<0.0001) in the maximal electroshock-induced seizure model. However, no significant decrease was noted in the duration of clonic convulsions in
a pentylenetetrazole-induced seizure model indicating lack of activity in petit mal epilepsy. The results of the present study indicate that artesunate at both the doses employed showed a significant anticonvulsant activity in the maximum electroshock-induced seizure model suggesting its potential utility in the management of generalized tonic-clonic seizures and partial seizures. Further studies regarding its mechanism of action are warranted.
Key words: Anticonvulsant, artesunate, neurotoxicity, pentylene tetrazole-induced seizures and maximum electroshockinduced

Full Text:



Breman JG, Alilio MS, Mills A. Conquering the intolerable burden

of malaria: What’s new, what’s needed: A summary. Am J Trop

Med Hyg 2004;71(2 Suppl):1-15.

Hein TT. An overview of the clinical use of artemisinin and its

derivatives in the treatment of falciparum malaria in Vietnam.

Trans R Soc Trop Med Hyg 1994;88S:7-8.

Harinasuta T, Karbwang J. Qinghaosu: A promising antimalarial.

J Am Med Assoc South East Asian edn 1994;34:7-8.

Ittarat W, Udomsangpeth R, Chotivanich KT, Looareesuwan S.

The effects of quinine and artesunate treatment on plasma tumor

necrosis factor levels in malaria-infected patients. Southeast Asian

J Trop Med Public Health 1999;30:7-10.

van Agtmael MA, Cheng-Qi S, Qing JX, Mull R, van Boxtel CJ.

Multiple dose pharmacokinetics of artemether in Chinese patients

with uncomplicated falciparum malaria. Int J Antimicrob Agents


Nontprasert A, Pukrittayakamee S, Dondorp AM, Clemens

R, Looareesuwan S, White NJ. Neuropathologic toxicity of

artemisinin derivatives in a mouse model. Am J Trop Med Hyg


Nontprasert A, Nosten-Bertrand M, Pukrittayakamee S,

Vanijanonta S, Angus BJ, White NJ. Assessment of the neurotoxicity

of parenteral artemisinin derivatives in mice. Am J Trop Med Hyg


Genovese RF, Petras JM, Brewer TG. Arteether neurotoxicity in the

absence of deficits in behavioral performance in rats. Ann Trop

Med Parasitol 1995;89:447-9.

Dayan AD. Neurotoxicity and artemisinin compounds: Do the

observations in animals justify limitations in clinical use? Med

Trop (Mars). 1998;58(3 Suppl):32-7.

Eweka AO, Adjene JO. Histological studies of the effects of oral

administration of artesunate on the superior colliculus of adult

wistar rats. Internet J Trop Med 2008;4:1-9

Perazzo FF, Carvalho JC, Carvalho JE, Rehder VL. Central

properties of the essential oil and the crude ethanol extract from

aerial parts of Artemisia annua L. Pharmacol Res 2003;48:497-502.

Salah SM, Jager AK. Two flavonoids from Artemisia herba-alba

Asso with in vitro GABAA-benzodiazepine receptor activity. J

Ethnopharmacol 2005;99:145-6.

Ghosh MN. Fundamentals of experimental pharmacology.

Calcutta: Scientific book agency; 1984. p. 154-5.

Swinyard EA. Laboratory evaluation of antiepileptic drugs. Review

of laboratory methods. Epilepsia 1969;10:107-19.

Brewer TG, Grate SJ, Peggins JO, Weina PJ, Petras JM, Levine BS,

et al. Fatal neurotoxicity of arteether and artemether. Am J Trop

Med Hyg 1994;51:251-9.

Karbwang J, Na-Bangchang K, Thanavibul A, Bunnag D,

Chongsuphajaisiddhi T, Harinasuta T. Comparison of oral

artesunate and quinine plus tetracycline in acute uncomplicated

falciparum malaria. Bull World Health Organ 1994;72:233-8.

Dondorp AM, Fanello CI, Hendriksen IC, Gomes E, Seni A,

Chhaganlal KD, et al. Artesunate versus quinine in the treatment

of severe falciparum malaria in African children (AQUAMAT):

An open-label, randomised trial. Lancet 2010;376:1647-57.

Duraisami R, Srinivasan D, Subramanian P. Anticonvulsant activity

of bioflavonoid gossypin. J Bangladesh Pharmacol Soc 2009;4:51-4.

Silambujanaki P, Chitra V, Kumari S, Sankari M, Raju D, Bala Tejo

Chandra Ch. Anti-convulsant activity of methanolic extract of

Butea monosperma leaves. Res J Pharm Biol Che Sci 2010;1:431-5.

Loscher W, Schmidt D. Which animal models should be used

in the search for new antiepileptic drugs? A proposal based on

experimental and clinical considerations. Epilepsy Res 1988;2:


Lehmann J, Hutchison AJ, McPherson SE, Mondadori C, Schmutz

M, Sinton CM, et al. CGS 19755, a selective and competitive

N-methyl-D-aspartate-type excitatory amino acid receptor

antagonist. J Pharmacol Exp Ther 1988;246:65-75.

Kulkarni SK, Mehta AK, Ticku MK. Comparison of anticonvulsant

effect of ethanol against NMDA-, kainic acid- and picrotoxininduced

convulsions in rats. Life Sci 1990;46:481-7.

DOI: https://doi.org/10.22377/ijgp.v6i1.240


  • There are currently no refbacks.