Evaluation of the seizure modifying potential of ondansetron in mice

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.

Pro-Convulsant Effect of Olanzapine, an Atypical Antipsychotic on Maximal Electro Shock Induced Seizures in Wistar Albino Rats.

Objectives: The aim of the study was to investigate the chronic effect of Olanzapine; an atypical antipsychotic drug on maximal electroshock (MES) induced seizures in Wistar albino rats. Methods: Olanzapine (2mg/kg, 10 days orally) was used to study its effect on MES induced seizures in Wistar albino rats. Duration of the tonic hind limb extension was noted. Results: Olanzapine (2mg/kg) significantly (p<0.001) increased the duration of hind limb extension induced by MES. Conclusions: The data suggests that Olanzapine, the atypical antipsychotic drug has a proconvulsant action.

Investigation of seizure activity after cyclic nucleotide phosphodiesterase inhibition with second messenger and calcium ion channel inhibition in mice.

The role of PDE-4 inhibitor etazolate, was evaluated in the presence of PDE-7 inhibitor, BRL-50481, in animal models of epilepsy. Seizures were induced in the animals by subjecting them to injection of chemical convulsants, Pilocarpine, Kainic acid (KA) and maximal electroshock (MES). The combination of etazolate and BRL50481 treated mice showed a significant (P<0.001) quick onset of action, jerky movements and convulsion when compared to gabapentin. The combination of etazolate and sGC inhibitor, methylene blue (MB) treated mice showed a significant (P<0.001) delay in onset of action, jerky movements and convulsion when compare to gabapentin as well as against the combination of etazolate with BRL 50481.The present study mainly highlights the individual effects of etazolate and combination with BRL-50481 potentiates (P<0.001) the onset of seizure activity against all models of convulsion. The study mainly comprises the onset of seizures, mortality/recovery, percentage of prevention of seizures (anticonvulsant) and total duration of convulsive time. The total convulsive time was prolonged significantly (P<0.05 and P<0.01) in combination of methylene blue with etazolate treated (28.59% and 35.15 %) groups, compared to DMSO received group (100%) in the MES model. In the same way, the combination of calcium channel modulator (CCM) and calcium channel blocker (CCB) amiodarone and nifedipine respectively, with etazolate showed a significant (P<0.001) delay in onset of seizures, compared to DMSO and etazolate treated groups in all models of epilepsy. This confirms that both CCM and CCB possess anticonvulsant activity. Finally, the study reveals that identification of new cAMP mediated phosphodiesterases family members offers a potential new therapy for epilepsy management in future.