Biochemical and clinical studies on epileptic patients during two phase I trials with the novel anticonvulsant taltrimide

Taltrimide (2-phthalimidoethanesulphon-N-isopropylamide), a lipophilic derivative of taurine and a potent anticonvulsant in animal studies, was administered in daily doses of 1 and 2 g for 2 weeks with an interval of 2.5 months in 2 phase I clinical trials to 9 drug-resistant epileptic patients. Seizures and EEG were recorded, and routine laboratory studies conducted. Concentrations of antiepileptic drugs in plasma, of Amino acids in urine and plasma, and contents of Amino acids, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and cyclic nucleotides in the cerebrospinal fluid were determined. Although no clinical or neurophysiological effects were observed, an increase in the cerebrospinal fluid contents of HVA and cyclic nucleotides and changes in the concentrations of antiepileptic drugs and Amino acids were found. The concentrations of HVA correlated with those of 5-HIAA and also with those of the main active metabolite of taltrimide. Biochemical changes due to taltrimide treatment resembled only partly those found after taurine treatment.