ralitoline and Epilepsy

Topics: Animals; Anticonvulsants; Brain; Drugs, Investigational; Electroencephalography; Epilepsy; Evoked Potentials; Humans; Thiazoles

The Third Eilat Conference on New Antiepileptic Drugs was held at the Royal Beach Hotel from May 27 to May 30, 1996. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss critical issues in drug development, new antiepileptic drugs (AEDs) in development, progress reports and recent findings of newly marketed AEDs, the use of AEDs in special populations and their utilization in non-epileptic disorders. Over the last seven years, six new AEDs have been introduced worldwide and new information on their safety and efficacy has become available. These include felbamate, gabapentin, lamotrigine, oxcarbazepine, topiramate and vigabatrin. Drugs in development include those at an advanced stage, such as remacemide and tiagabine, as well as those just entering clinical trials, such as rufinamide (CGP 331010) and levetiracetam (ucb LO59). The following is a summary of the presentations for drugs in development and recent findings on newly marketed drugs.

Topics: Acetamides; Animals; Anticonvulsants; Azetidines; Carbamates; Drug Evaluation, Preclinical; Drugs, Investigational; Epilepsy; Humans; Israel; Levetiracetam; Nipecotic Acids; Phenylenediamines; Piracetam; Product Surveillance, Postmarketing; Randomized Controlled Trials as Topic; Thiazoles; Tiagabine; Triazoles

Ralitoline and CI-953 are anticonvulsant compounds active in both maximal electroshock and kindling models of seizures with rodents. CI-953 (IC50 = 5 microM) and ralitoline (IC50 = 2 microM) both blocked sustained repetitive firing of sodium action potentials with effects on firing activity triggered by spontaneous excitatory postsynaptic potentials at higher concentrations. No effects on iontophoretic GABA and glutamate responses were noted. Both compounds inhibited the binding of tritiated batrachotoxinin A 20-alpha-benzoate ([3H]BTX-b) to rat brain synaptosomes with apparent Kd values of 29 microM (CI-953) and 25 microM (ralitoline). Our results suggest that effects on voltage-dependent sodium channels may underlie the anticonvulsant action of these compounds.

Topics: Action Potentials; Animals; Anticonvulsants; Batrachotoxins; Carbamazepine; Cells, Cultured; Electrophysiology; Epilepsy; Kinetics; Mice; Neurons; Phenylurea Compounds; Phenytoin; Radioligand Assay; Sodium Channels; Spinal Cord; Synaptosomes; Thiazoles