Low propensity of conventional antiepileptic drugs for interaction with felbamate against maximal electroshock-induced seizures in mice

The objective of this study was to evaluate an interaction of the novel antiepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with conventional antiepileptic drugs against maximal electroshock-induced convulsions in mice. Electroconvulsions were produced by means of an alternating curr...

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Bibliographic Details
Published in:Journal of Neural Transmission 2000-01, Vol.107 (7), p.733-743
Main Authors: BOROWICZ, K. K, STASIUK, G, TETER, J, KLEINROK, Z, GASIOR, M, CZUCZWAR, S. J
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - blood
Anticonvulsants - pharmacokinetics
Anticonvulsants. Antiepileptics. Antiparkinson agents
Avoidance Learning - drug effects
Biological and medical sciences
Brain - metabolism
Drug Interactions
Electroshock
Female
Medical sciences
Mice
Motor Skills - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Phenylcarbamates
Propylene Glycols - blood
Propylene Glycols - pharmacokinetics
Seizures - etiology
Seizures - metabolism
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Summary:The objective of this study was to evaluate an interaction of the novel antiepileptic drug felbamate (2-phenyl-1,3-propanediol dicarbamate) with conventional antiepileptic drugs against maximal electroshock-induced convulsions in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, 0.2-s stimulus duration, tonic hindlimb extension taken as the endpoint). Adverse effects were evaluated in the chimney test (motor performance) and passive avoidance task (long-term memory). Brain and plasma levels of antiepileptic drugs were measured by immunofluorescence. Felbamate (7.5-30 mg/kg) significantly increased the electroconvulsive threshold. Felbamate at the subprotective dose of 5 mg/kg did not affect the anticonvulsive action of antiepileptics studied. On the other hand, this drug used at the lowest protective dose of 7.5mg/kg remained without effect upon the activity of valproate, carbamazepine or phenobarbital, but significantly potentiated the protective potential of diphenylhydantoin. No adverse effects were observed with combinations of felbamate with these antiepileptics. Neither brain nor free plasma levels of antiepileptic drugs were changed by felbamate. The results indicate that the combination of felbamate with conventional antiepileptic drugs is not promising from the experimental point of view.
ISSN:0300-9564
1435-1463
DOI:10.1007/s007020070055