Pharmaco-EEG studies with fluperlapine

Abstract

In the first of 2 studies, the effects of 3-fluoro-6-(4-methyl-piperazinyl)- 11H -dibenz[b,e]azepine ( fluperlapine , NB 106-689) 5 and 10 mg, clozapine 5 and 10 mg, and placebo on the EEG and on subjective mental and emotional state were investigated in 8 healthy male volunteers. The study was carried out as a double-blind within-subject comparison, with randomized sequence of treatments. Quantitative spectral analysis of the EEG revealed that changes after fluperlapine were strikingly similar to those after clozapine, i.e. an increase in delta and theta and a decrease in alpha activity. These changes were associated with a reduction in self-rated "wakefulness" and are evidence of a sedative effect. The drugs' effects differed only in the magnitude of the increase in beta activity in the 20-40 cps frequency band (beta 2), which was greater after fluperlapine than after clozapine. Since increased beta 2 activity has been reported with tricyclic antidepressants, it is suggested that fluperlapine , besides possessing neuroleptic properties, might also have some properties of a (sedative) antidepressants. It is estimated from the EEG findings that, at equal doses, fluperlapine (capsules) has approximately one half of the sedative potency of clozapine (tablets). A second study in schizophrenic patients revealed strong correlations between EEG effects and blood levels of unchanged fluperlapine during long-term treatment.