2-Chloro-N(6)-cyclopentyladenosine enhances the anticonvulsant action of carbamazepine in the mouse maximal electroshock-induced seizure model.
Journal Title: Pharmacological Reports - Year 2005, Vol 57, Issue 6
Abstract
This study examines the anticonvulsant profile of interactions between 2-chloro-N(6)-cyclopentyladenosine (CCPA, a selective adenosine A(1) receptor agonist) and four conventional antiepileptic drugs (AEDs: carbamazepine - CBZ, phenobarbital, phenytoin and valproate) in the mouse maximal electroshock seizure (MES) model. Acute adverse effects produced by AEDs in combination with CCPA were determined in the chimney test (motor performance) and passive avoidance task (long-term memory). Results indicate that CCPA administered alone at 0.25 and 0.5 mg/kg significantly elevated the electroconvulsive threshold in mice. Additionally, the agent at a sub-threshold dose of 0.125 mg/kg potentiated the anticonvulsant activity of CBZ by reducing its ED(50) in the MES test from 11.2 to 7.7 mg/kg (p < 0.01). In contrast, 8-cyclopentyl-1,3-dimethylxanthine (DPCPX, a selective adenosine A(1) receptor antagonist at 5 mg/kg) abolished the enhanced anticonvulsant effects offered by the combination of CBZ with CCPA (0.125 mg/kg). Moreover, CCPA (0.125 mg/kg) co-administered with other tested AEDs had no significant impact on their antiseizure properties in the MES test in mice. Neither CCPA (0.125 mg/kg) administered singly, nor in combinations with conventional AEDs (at their ED(50)s) affected motor performance in the chimney test and long-term memory in the passive avoidance task. No pharmacokinetic alterations in brain CBZ concentrations were observed after administration of CCPA at 0.125 mg/kg. It may be concluded that CCPA, acting selectively on adenosine A(1) receptors, enhances pharmacodynamically the antiseizure effect of CBZ in the MES test.
Authors and Affiliations
Jarogniew Łuszczki, Maria Kozicka, Mariusz Świąder, Stanisław Czuczwar
Keywords
Related Articles
- EP ID EP82315
- DOI -
- Views 136
- Downloads 0
Gastric anti-ulcerative and anti-inflammatory activity of metyrosine in rats.
In this study, the anti-inflammatory and anti-ulcerative effects of metyrosine, a selective tyrosine hydroxylase enzyme inhibitor, were investigated in rats. For ulcer experiments, indomethacin-induced gastric ulcer test...
Lymphocyte-suppressing, endothelial-protective and systemic anti-inflammatory effects of metformin in fenofibrate-treated patients with impaired glucose tolerance.
Background: No previous clinical study has been designed to assess the additive effect of metformin and a fibrate on lymphocyte secretory function. The aim of our study was to investigate whether metformin produces any e...
Effect of licofelone against mechanical hyperalgesia and cold allodynia inthe rat model of incisional pain.
Hyperalgesia from an incisional pain is evoked by noxious stimuli (mechanicaland cold). The present study was aimed to examine the effect of licofelone, a dual inhibitor of cyclooxygenases(COX-1/COX-2) and 5-lipoxygenase...
Statin-induced myopathies.
Statins are considered to be safe, well tolerated and the most efficient drugs for the treatment of hypercholesterolemia, one of the main risk factor for atherosclerosis, and therefore they are frequently prescribed medi...
Detrimental effect of postnatal blockade of N-methyl-D-aspartate receptors on sensorimotor gating is reversed by neuroleptic drugs.
Postnatal hypofunction of N-methyl-D-aspartate (NMDA) receptors leads to several behavioral deficits in adult rats resembling deficits typical of schizophrenia-like deficits of sensorimotor gating. Thus far, it is not kn...