Pharmaco-EEG profile of levoprotiline: second example to discuss the predictive value of pharmaco-electroencephalography in early human pharmacological evaluations of psychoactive drugs.

The present paper forms the second part of a critical evaluation of the use of pharmaco-EEG as an instrument for assessing the profile of action of psychoactive drugs in man based on the trial results of three new psychoactive test substances. Part I described the basic principles and methodological approaches and illustrated the value of pharmaco-EEG in framing hypotheses about the therapeutic efficacy of psychotropic drugs by the example of the neuroleptic drug savoxepine. This chapter illustrates the relevance of pharmaco-EEG in the assessment of psychoactive drugs by reference to the test substance levoprotiline. Levoprotiline is the pure R-(-)-enantiomer of the racemic drug oxaprotiline, a successor to the second-generation antidepressant maprotiline. Only the S-(+)-enantiomer of oxaprotiline inhibits the re-uptake of noradrenaline. In view of the absence of any monoamine-uptake inhibiting action of levoprotiline, this drug was assumed to be devoid of an antidepressive action. This assumption, however, was disproved by observations made in clinical studies with depressive patients, in whom levoprotiline did indeed display antidepressive activity. Investigations of levoprotiline in the pharmaco-EEG model--even though being retrospective in the sequence of events--would have been able to produce objective prediction of antidepressive potential in man. The substance was tested by comparison to placebo and to the standard antidepressant imipramine in nine young, healthy male volunteers. The experimental design was a cross-over uncompleted block design with three consecutive trial days one week apart.(ABSTRACT TRUNCATED AT 250 WORDS)