title: Clinical trial with an experimental taurine derivative, taltrimide, in epileptic patients.
abstract: The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2-week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood-brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has proconvulsive properties in humans.
authors.forename: K
authors.initials: K
authors.lastname: Koivisto
authors.forename: J
authors.initials: J
authors.lastname: Sivenius
authors.forename: T
authors.initials: T
authors.lastname: Keränen
authors.forename: J
authors.initials: J
authors.lastname: Partanen
authors.forename: P
authors.initials: P
authors.lastname: Riekkinen
authors.forename: G
authors.initials: G
authors.lastname: Gothoni
authors.forename: O
authors.initials: O
authors.lastname: Tokola
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
mesh_terms: D000328:Adult; D002220:Carbamazepine / Q000097:blood / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D002998:Clonazepam / Q000097:blood / Q000627:therapeutic use; D004569:Electroencephalography; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007211:Indoles / Q000097:blood / Q000627:therapeutic use*; D010634:Phenobarbital / Q000097:blood / Q000627:therapeutic use; D010672:Phenytoin / Q000097:blood / Q000627:therapeutic use; D010797:Phthalimides; D014635:Valproic Acid / Q000097:blood / Q000627:therapeutic use
chemical_list: D007211:Indoles; D010797:Phthalimides; D002220:Carbamazepine; D002998:Clonazepam; D014635:Valproic Acid; D010672:Phenytoin; C046932:taltrimide; D010634:Phenobarbital