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
Effect of metyrapone on the fluoxetine-induced change in extracellular dopamine, serotonin and their metabolites in the rat frontal cortex.
Major depression is frequently associated with the hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. Metyrapone (an i...
Exendin-4 and GLP-1 decreases induced expression of ICAM-1, VCAM-1 and RAGE in human retinal pigment epithelial cells.
Advanced glycation end products (AGEs) take part in the development of diabetic retinopathy. Hyperglycemia triggers an inflammatory response in the retina. These mechanisms may lead to an enhanced expression of adhesion...
Important role of 3-methoxytyramine in the inhibition of cocaine sensitization by 1-methyl-1,2,3,4-tetrahydroisoquinoline: an in vivo microdialysis study.
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous compound with neuroprotective and antidopaminergic activities. Our previous research has shown that 1MeTIQ prevents morphine addiction and abates the expr...
Effects of escin on acute inflammation and the immune system in mice.
Escin has been used extensively to treat chronic venous insufficiency, hemorrhoids, and edema resulting from cerebral ischemic damage, trauma or operation. However, no studies have looked at the anti-inflammatory propert...
New antinociceptive agents related to dihydrosphingosine.
The main objective of this study was to evaluate the antinociceptive activity of three ethylenediamine derivatives and three β-aminoethanol lipidic derivatives structurally related to dihydrosphingosine. These derivative...