Amelioration of caffeine-induced seizures by modulators of sigma, N-methyl-d-Aspartate and ryanodine receptors in mice

Abstract

BackgroundSigma receptors, N-methyl-D-aspartate (NMDA) antagonist, and modulators of intracellular calcium may be useful for seizure control. Therefore, we aimed to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, against pentylenetetrazole (PTZ)-induced seizures in mice and assess ketamine and caffeine interaction with the antiepileptic effects of opipramol.MethodsPTZ (100 mg/kg) was used for the induction of seizure in 72 male albino Swiss strain of mice (n=8). Opipramole (10, 20, and 50 mg/kg), ketamine (50 mg/kg), caffeine (200 mg/kg), opipramole (20 mg/kg) plus ketamine (50 mg/kg), opipramole (20 mg/kg) plus caffeine (200 mg/kg), diazepam (5 mg/kg as a positive control), and the vehicle were administered interaperitoneally 30 minutes before the injection of PTZ. The latency was recorded for the clonic, tonic-clonic seizures, and death of animals after the injection of PTZ. Kruskal-Wallis test followed by Dunn’s test was used for the analysis of data. Statistical analysis was performed with the SPSS software version 23.0 and P<0.05 was considered as the significant level.ResultsOpipramol (20 mg/kg) increased the latency for the PTZ-induced clonic (44%, P=0.021) and tonic-clonic (130.80%, P=0.043) seizures compared with the vehicle-treated group. Animals treated with opipramol (20 mg/kg) plus caffeine (200 mg/kg) had a significantly higher onset of PTZ-induced clonic and tonic-clonic seizures compared with the control (P=0.046 and <0.001, respectively). Ketamine combined with opipramol increased the onset of tonic-clonic seizure compared with the vehicle-treated groups (P<0.001).ConclusionOpipramol attenuated the seizures induced by the PTZ. Ketamine and caffeine had no effect on the anticonvulsant activity of opipramol.

Pharmacological Analysis of GABAA Receptor and Sigma1R Chaperone Interaction: Research Report I―Investigation of the Anxiolytic, Anticonvulsant and Hypnotic Effects of Allosteric GABAA Receptors’ Ligands

“…It also shortened the falling asleep time (5 mg/kg PRE-084) and prolonged pentobarbital-induced sleep duration (1 and 5 mg/kg PRE-084). Similarly, prior single administration of the non-selective Sigma1R ligand opipramol, which has anxiolytic properties [58], also increased the latency of the PTZ-induced clonic seizures [59]. The data on the attenuation of seizures by Sigma1R ligands with agonist properties [60] are consistent with the results obtained in the anhedonia modeling with the proconvulsive GABA A R antagonist picrotoxin.…”

Farelerde Pentilenetetrazol ile İndüklenen Epilepsi Modelinde Agmatinin Etkilerinin ve Nitrik Oksitin Katkısının Araştırılması

“…PTZ blocks the GABA-mediated inhibition by binding to the GABA receptor complex on the picrotoxin site and therefore it leads to disinhibition. The activation of NMDA receptors (26), the inhibition of GABA and/or adenosine seem to be responsible for the initiation and generalization of PTZ-induced seizures. Studies reported that NO levels were increased in mice brain in PTZ-induced epilepsy (27)(28)(29).…”

Consecutive Controlled Case Series on Effectiveness of Opipramol in Severe Sleep Bruxism Management—Preliminary Study on New Therapeutic Path

“…It is interesting to note that sigma receptors can also be involved in Parkinson’s disease [ 42 ]. In addition, these receptors were reported to exhibit anticonvulsant activity [ 43 ]. Taking into account the sigma receptors, previously studied amitriptyline is also a sigma-1 receptor agonist [ 44 ], but with a lower affinity than opipramol [ 45 ].…”