DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20184321

Evaluation of the seizure modifying potential of ondansetron in mice

Nisharani Jadhav, Ravikumar Baradol, Manisha Bhosale

Abstract


Background: The aim of the study was to evaluate the seizure modifying potential of Ondansetron in experimental models of seizures in mice.

Methods: Mice were treated with three different doses of ondansetron i.p., at 3mg/kg, 6mg/kg and 8mg/kg and control group received normal saline 0.1 ml i.p. for 3 days. On 3rd day, mice were subjected to MES, of different strength half an hour after ondansetron administration and findings were recorded. The minimum threshold current at which tonic hind limb extension occurred was recorded. Each animal was observed for incidence and duration of tonic hind limb extension and the strength of current was noted. In PTZ model, mice were subjected to subconvulsive dose of PTZ 45mg/kg and convulsive dose of PTZ 60mg/kg. The incidence and onset of convulsion at 45 and 60mg/kg dose of PTZ were recorded.

Results: Mice receiving ondansetron 3mg/kg, showed significant decrease in duration of tonic hind limb extension at convulsive current strength of 50mA (p<0.001). While group receiving 6mg/kg, showed decrease in seizure threshold. (40mA current strength) Mice receiving 3mg/kg, showed significant increase in onset of seizures (p<0.001) at convulsive 60mg/kg dose of PTZ. While mice receiving 6mg/kg showed decrease in seizure threshold at sub convulsive 45mg/kg dose of PTZ. Group receiving 8mg/kg ondansetron, showed 100% mortality due to convulsions caused by ondansetron.

Conclusions: Ondansetron at low therapeutic dose (3mg/kg) has an anticonvulsant action, while it has a proconvulsant action at a high therapeutic dose (6mg/kg). Ondansetron causes convulsions at toxic dose (8mg/kg). So, care should be taken while giving ondansettron in high doses to prevent chemotherapy induced emesis.


Keywords


Anticonvulsant, Ondansetron, Proconvulsant, Seizures

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References


Goodman and Gilman’s The Pharmacological Basis of Therapeutics, Laurence L. Brunton, Eleventh Edition; 2006:1003-1005.

Ye JH, Ponnudurai R, Schaefer R Ondansetron: a selective 5-HT3 receptor antagonist and its applications in CNS-related disorders CNS Drug Rev. Summer. 2001;7(2):199-213.

Wilde MI, Markham A. Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Drugs. 1996 Nov;52(5):773-94.

Swain TR, Mohanty M. Letter to editor; Anticonvulsant action of Ondansetron; in Ind J Pharmacol. 1999;31:157.

Bagdy G, Kecskemeti V, Riba P, Jakus R. Serotonin and epilepsy. J Neurochem. 2007 Feb;100(4):857-73.

Sharma A, Raina V. Generalised seizures following ondansetron. Annals of Oncology. 2001 Jan;12(1):131-2.

Gener B, Burns JM, Griffin S, Boyer EW. Administration of ondansetron is associated with lethal outcome. Pediatrics. 2010 Apr 27:peds-2009.

Anonymous, Gastrointestinal drugs; Ondansetron; Editor Sweetman SC. Martindale: The Complete Drug Reference. 36th Ed. London: Pharmaceutical Press; 2009:1756-1758.

Reeta KH, Handu SS, Sharma D, Bhargava VK. Effects of 5HT3 antagonist ondansetron on learning and memory in rats. Ind J Pharmacol. 1999 Jul 1;31(4):285-9.

Anti convulsive Activity, editor Wolgang Vogel. Drug Discovery and Evaluation: Pharmacological assays, 3rd Edition, Springer publication; 2008:613-614.

Gupta SK. Antiepileptis. In Drug Screening methods (preclinical evaluation of new drugs). Editor SK Gupta. 2nd ed.; Jaypee publication; 2009;411-412.

Gasior M, Yankura J, Hartman AL, French A, Rogawski MA. Anticonvulsant and proconvulsant actions of 2‐deoxy‐d‐glucose. Epilepsia. 2010 Aug;51(8):1385-94.

Akula KK, Dhir A, Kulkarni SK. Pro-convulsant effect of cefazolin sodium against pentylenetetrazol-or picrotoxin-induced convulsions in mice.

De Wit R, Aapro M, Blower PR: Is there a pharmacological basis for differences in 5-HT3-receptor antagonist efficacy in refractory patients? Cancer Chemother Pharmacol. 2005;56(3):231-8.

Gholipour T, Mojtahed A, Dehpour AR. The 5-HT3 receptor antagonist granisetron lowers clonic seizure threshold in pentylenetetrazole induced seizure in mice: The involvement of nitric oxide system. Neurology Asia. 2007;12 (Supplement 1):110.

Gholipour T, Ghasemi M, Riazi K, Ghaffarpour M, Dehpour AR. Seizure susceptibility alteration through 5-HT3 receptor: modulation by nitric oxide. Seizure. 2010 Jan 1;19(1):17-22.