Effect of caffeine on the anticonvulsant effects of oxcarbazepine, lamotrigine and tiagabine in a mouse model of generalized tonic-clonic seizures.
Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 5
Abstract
Caffeine has been reported to be proconvulsant and to reduce the anticonvulsant efficacy of a variety of antiepileptic drugs (carbamazepine, phenobarbital, phenytoin, valproate and topiramate) in animal models of epilepsy and to increase seizure frequency in patients with epilepsy. Using the mouse maximal electroshock model, the present study was undertaken so as to ascertain whether caffeine affects the anticonvulsant efficacy of the new antiepileptic drugs lamotrigine, oxcarbazepine and tiagabine. The results indicate that neither acute nor chronic caffeine administration (up to 46.2 mg/kg) affected the ED(50) values of oxcarbazepine or lamotrigine against maximal electroshock. Similarly, caffeine did not modify the tiagabine electroconvulsive threshold. Furthermore, caffeine had no effect on oxcarbazepine, lamotrigine and tiagabine associated adverse effects such as impairment of motor coordination (measured by the chimney test) or long-term memory (measured by the passive avoidance task). Concurrent plasma concentration measurements revealed no significant effect on lamotrigine and oxcarbazepine concentrations. For tiagabine, however, chronic caffeine (4 mg/kg) administration was associated with an increase in tiagabine concentrations. In conclusion, caffeine did not impair the anticonvulsant effects of lamotrigine, oxcarbazepine, or tiagabine as assessed by electroconvulsions in mice. Also, caffeine was without effect upon the adverse potential of the studied antiepileptic drugs. Thus caffeine may not necessarily adversely affect the efficacy of all antiepileptic drugs and this is an important observation.
Authors and Affiliations
Magdalena Chrościńska-Krawczyk, Neville Ratnaraj, Philip Patsalos, Stanisław Czuczwar
Keywords
Related Articles
- EP ID EP91570
- DOI -
- Views 125
- Downloads 0
Melatonin in experimental seizures and epilepsy.
Although melatonin is approved only for the treatment of jet-lag syndrome and some types of insomnia, clinical data suggest that it is effective in the adjunctive therapy of osteoporosis, cataract, sepsis, neurodegenerat...
Oleanolic acid derivative methyl 3,11-dioxoolean-12-en-28-olate targets multidrug resistance related to ABCB1.
Multidrug resistance (MDR) in leukemia patients is a great incentive to the development of new drugs. In a search for potential multidrug resistance modulators we tested a group of oleanolic acid (OA) analogues modified...
Antinociceptive activity of sildenafil and adrenergic agents in the writhing test in mice.
The authors investigated the antinociceptive activity of sildenafil and adrenergic agents co-administered in the writhing test in mice. The intensity of nociception was quantified by the number of writhes occurring betwe...
New conjugates of muramyl dipeptide and nor-muramyl dipeptide linked to tuftsin and retro-tuftsin derivatives significantly influence their biological activity.
The synthesis and biological activity of new conjugates of muramyl dipeptide (MDP) and nor-muramyl dipeptide (nor-MDP) with tuftsin and retro-tuftsin derivatives containing isopeptide bond between ε-amino group of lysine...
Retigabine: the newer potential antiepileptic drug.
Retigabine represents an antiepileptic drug possessing a completely different mechanism of action when compared to the existing classical and newer antiepileptic drugs. In the therapeutic range, retigabine enhances potas...