Antikonvulsivni ucinky zesileni GABAergni inhibice v prubehu ontogenese.

The thesis summarizes some recent data of our laboratory on developmental pharmacology of antiepileptics. The action of drugs potentiating GABAergic inhibition by different mechanisms was tested in a model of motor seizures induced by a subcutaneous injection of pentylenetetrazol in five age groups of rats. This model allows to evaluate drug action on two different types of seizures, minimal clonic and generalized tonic-clonic and we have our own data for all classical and many potential antiepileptic drugs with different mechanisms of action for comparison. The generalization of the results is rather complicated and this opinion is supported by our data with other models of epileptic seizures. Present data demonstrate clearly both quantitative and qualitative age-bound changes of anticonvulsant action of studied drugs. Quantitative changes may be mainly due to maturation of the drugs pharmacokinetics but pharmacodynamic changes cannot be excluded. Data about quantitative changes may serve for an exact dosage of drugs at different developmental stages. On the other hand, there are clear-cut qualitative developmental changes of some new antiepiletptic drugs - e.g. benzodiazepine partial agonist Ro 19-8022 and tiagabine as drugs with a single mechanism of action and topiramate as a drug with multiple mechanisms of action. These data may be used for a prediction of spectrum of efficacy of antiepileptic drugs during development.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi