Pharmaco-EEG study of 6-azaianserin (ORG 3770): Dissociation of EEG and pharmacologic predictors of antidepressant activity

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Abstract
The effects of a single oral dose of 6-azamianserin (2 mg) were compared to those of mianserin (6 mg), flurazepam (10 mg), and placebo in 11 healthy male volunteers, in a crossover design. Quantitative EEG, heart rate, blood pressure, task performance, and subjective state were measured. EEG and behavioral measures distinguished the substances from placebo. 6-Azamianserin was similar to mianserin in type and duration of effects. In a separate study in 12 volunteers, 0.5 and 1.0 mg of the (+) and (-) enantiomers of 6-azamianserin elicited dose-related EEG and behavioral effects, distinguishable from placebo. These effects were similar to those elicited by racemic 6-azamianserin and mianserin. Clinical trials of 6-azamianserin in depressed patients, particularly the elderly and those with cardiovascular disease, are warranted. Dosages selected should be onethird those of mianserin. The stereospecific properties of the enantiomers in preclinical tests predict that any clinical ‘antidepressant’ activity will reside in the (+) isomer only, while the pharmaco-EEG trials predict that both enantiomers will be clinically ‘antidepressant”. Clinical testing of the isomers, particularly the (-) isomer, is indicated as a test of the predictive value of pharmacologic and pharmaco-EEG models of clinical antidepressant activity.