Acute exposure to caffeine decreases the anticonvulsant action of ethosuximide, but not that of clonazepam, phenobarbital and valproate against pentetrazole-induced seizures in mice.
Journal Title: Pharmacological Reports - Year 2006, Vol 58, Issue 5
Abstract
This study examines the effect of acute administration of caffeine sodiumbenzoate (CAF) on the anticonvulsant action of four conventional antiepileptic drugs (AEDs: clonazepam - CZP, ethosuximide - ETS, phenobarbital - PB and valproate - VPA) against pentetrazole (PTZ) -induced clonic seizures in mice. The results indicate that CAF at a dose of 92.4 mg/kg significantly reduced the threshold for PTZ-induced clonic seizures in mice from 69.5 to 51.7 mg/kg (p < 0.05), being ineffective at lower doses of 69.3 and 46.2 mg/kg. Moreover, CAF at doses of and 92.4 mg/kg attenuated the protective action of ETS against PTZ-induced seizures, by increasing its median effective dose (ED(50)) from 127.7 to 182.3 (p < 0.05), and 198.3 mg/kg (p < 0.01), respectively. In this case, no pharmacokinetic changes in total brain ETS concentrations after systemic ip administration of CAF (at 92.4 mg/kg) were observed, indicating a pharmacodynamic nature of interaction between ETS and CAF in the PTZ-test in mice. In contrast, CAF (at a dose of 92.4 mg/kg reducing the threshold for PTZ-induced seizures) combined with other AEDs (CZP, PB and VPA) did not affect their anticonvulsant action in the PTZ test in mice. Moreover, CAF (92.4 mg/kg) did not alter significantly total brain concentrations of the remaining AEDs (CZP, PB and VPA). The evaluation of potential acute adverse effects produced by AEDs in combination with CAF revealed that neither CAF (up to 92.4 mg/kg) administered alone nor combined with the studied drugs (at doses corresponding to their ED(50) values in the PTZ-test) affected motor performance of animals in the chimney test. In conclusion, the acute exposure to CAF may diminish the antiseizure protection offered by ETS in epileptic patients. Therefore, patients treated with ETS should avoid CAF.
Authors and Affiliations
Jarogniew Łuszczki, Marek Zuchora, Katarzyna Sawicka, Justyna Kozińska, Stanisław Czuczwar
Keywords
Related Articles
- EP ID EP144392
- DOI -
- Views 93
- Downloads 0
Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat.
The current knowledge on the involvement of cytochrome P450 (P450, CYP) isoforms in the metabolism of caffeine in rat and human liver is reviewed. Attention is also paid to species- and concentration-dependent metabolism...
Perazine at therapeutic drug concentrations inhibits human cytochrome P450 isoenzyme 1A2 (CYP1A2) and caffeine metabolism - an in vitro study.
The aim of the present study was to estimate the inhibitory effect of perazine, a phenothiazine neuroleptic with piperazine structure in a side chain, on human CYP1A2 activity measured as a rate of caffeine 3-N- and 1-N-...
Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.
In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplement...
Cannabinoid CB1 receptors in rat medial prefrontal cortex are colocalized with calbindin- but not parvalbumin- and calretinin-positive GABA-ergic neurons.
In the present study, we investigate putative localization of cannabinoid receptors 1 (CB1) protein on a population of cortical gamma-aminobutyric acid (GABA) - positive interneurons characterized by expression of calciu...
Biotechnology and genetic engineering in the new drug development. Part II. Monoclonal antibodies, modern vaccines and gene therapy.
Monoclonal antibodies, modern vaccines and gene therapy have become a major field in modern biotechnology, especially in the area of human health and fascinating developments achieved in the past decades are impressive e...