Effect of Sabeluzole (R 58 735) on Memory Functions in Patients with Epilepsy

Abstract

Sabeluzole, a new benzothiazol derivative, has shown positive effects on memory function in animals and in normal volunteers. The present study reports the results of sabeluzole, in memory-impaired patients with localization-related (partial) epilepsy. A randomized, double-blind placebo-controlled parallel-group design was used. A total of 38 patients entered a prospective baseline. Five patients dropped out from the study, thus 33 patients were randomly assigned to either a 12-weeks treatment with sabeluzole (n = 14) or placebo (n = 19). The treatment phase was preceded by a titration phase of 4 weeks to obtain serum levels of sabeluzole between 50 and 130 ng/ml. In order to maintain blindness, a sham titration was carried out in the placebo group. The number of ‘responders’, i.e. patients with a > 1 SD improvement on at least three of the memory tests was 9 out of 14 (64.3%) in the sabeluzole group and 7 out of 19 (36.8%) in the placebo group. This suggests a clinically relevant effect of sabeluzole. The analysis of the memory tests showed a statistically significant improvement with sabeluzole on the verbal long-term memory test. This could represent a specific drug effect and is in line with previous results of normal volunteer studies that also found improvement mainly restricted to the area of verbal long-term memory.

Neuropharmacological Aspects of Cognitive Neurorehabilitation in Epilepsy

“…A randomized, double-blind placebo-controlled parallel-group study of 38 patients with epilepsy, assigned to a 12 week treatment with either sabeluzole or placebo showed a number of responders (patients with an improvement that was more than 1 SD on at least three of the memory tests) in the sabeluzole group (64%), which was nearly twice the number of responders in the placebo group (36%) [2]. This suggested a potentially clinically relevant effect of sabeluzole in the memory problems associated with epilepsy, and its effect on long-term verbal memory tests may represent a specific drug effect.…”

“…However, the evidence, taken together, is not clear as to whether sabeluzole improves memory function per se or reactivates or restores less specific impaired cognitive function. Although the mechanism of action of sabeluzole is not completely clear, its role in improving fast axonal transport and the effect on voltage-dependent outward K+ currents may play a role in its cognitive effects [2].…”