Role of cinnarizine and nifedipine on anticonvulsant effect of sodium valproate and carbamazepine in maximal electroshock and pentylenetetrazole model of seizures in mice

Abstract

Objective:To study the effect of calcium channel blockers (CCBs) cinnarizine and nifedipine on maximal electroshock (MES)-induced and pentylenetetrazole (PTZ)-induced convulsions and also their effect in combination with conventional antiepileptic drugs (CAED).Materials and Methods:For this study, Swiss albino mice were used. Effects of cinnarizine (30 mg/kg), nifedipine (5 mg/kg), sodium valproate (300 mg/kg) and carbamazepine (8 mg/kg) alone and in combination were studied in MES and PTZ seizure models. Abolition of hind limb tonic extension was an index of anticonvulsant activity in MES, while for PTZ seizures, failure to observe even a single episode of tonic spasm for 5 s duration for 1 h was the index. With this, percentage protection was calculated and statistical analysis was carried out using Fisher’s exact test (Ovvind Langsrud software, German version).Results:In MES seizures, augmented effects were obtained when cinnarizine was combined with sodium valproate, i.e. 100%. In PTZ-induced seizures, augmented effects were obtained when nifedipine was combined with sodium valproate, i.e. 100%. Thus, cinnarizine added to sodium valproate therapy produces significant protection against MES seizures while nifedipine added to sodium valproate therapy produces significant protection against PTZ seizures.Conclusion:The results provide a lead for potential benefit of adding CCBs to sodium valproate in the treatment of epilepsy, which needs to be explored further.

Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice

“…We selected VA for this study as it is one of the oldest and most commonly prescribed anticonvulsants in humans (Meunier et al, 1963 ; Pinder et al, 1977 ; Tunnicliff, 1999 ; Who Model List of Essential Medicines, 2013 ; reviewed by Perucca, 2002 ). We applied VA at a dose (300 mg/kg) that doesn't change behavior or EEG activity (Roucard et al, 2010 ) but has protective effect in mice (Brahmane et al, 2010 ; Löscher et al, 2013 ); injected systemically with a single dose of KA (Abdel-Rahmanm et al, 1999 ). We selected the KA seizure induction model as it is one of the most widely used model of seizures that mimics the features and pathophysiology of temporal lobe epilepsy in humans (reviewed by Ben-Ari, 1985 ; Fisher, 1989 ; Vincent and Mulle, 2009 ; Lévesque et al, 2016 ).…”

Structure-Based Virtual Screening Identifies Novobiocin, Montelukast, and Cinnarizine as TRPV1 Modulators with Anticonvulsant Activity In Vivo

“… a Number of animals protected relative to the total number of animals tested. b Number of animals with neurotoxic effects relative to the total number of animals tested. c a ; b ; c ; d ; e ; f ; g ; h d For each test drug, negative control mice received the correspondent vehicle while positive control mice received an anticonvulsant drug with known activity in each seizure model, as described individually for each in vivo assay under Section . …”

“…CNZ, along with other members of the calcium channel blockers, has demonstrated anticonvulsant activity in different animal models of seizures including MES, PTZ, and audiogenic induced seizures. − However, its anticonvulsant activity in the 6 Hz test had not been previously evaluated. Our studies suggest no activity in this model, at least at the dose tested (30 mg/kg).…”

Solubilization and co-solubilization of carbamazepine and nifedipine in mixed micellar systems: insights from surface tension, electronic absorption, fluorescence and HPLC measurements

“…Flunarizine, a CCB, was given along with antiepileptic drugs as an add-on therapy and has been found to reduce seizure signicantly, 36 and nifedipine (NFD) was given along with carbamazepine (CBZ) to provide superior seizures control in maximal electroshock (MES)induced and pentylenetetrazole (PTZ)-induced convulsions. 37 There are reports where a patient with classical pattern of bipolar disorder with cycles of mania and depression responds to a combination of CBZ and NFD. 38 In our earlier work 29 we demonstrated that the single and simultaneous solubilization of CBZ and NFD in a single surfactant based micellar media is highly sensitive to the hydrophilic-lipophilic balance (HLB) value and the concentration of surfactants.…”