Assessment of the antidepressant activity of dothiepin and its metabolites by preclinical tests

Abstract

The affinities of dothiepin and its principal metabolites northiaden, dothiepin sulphoxide and northiaden sulphoxide for [3H]imipramine binding sites in the rat cortical homogenates, and for [3H]spiperone and [3H]serotonin receptor sites in preparations from the rat frontal cortex and hippocampus were studied. As inhibitors of [3H]imipramine binding, the strengths of the drugs are, in terms of their IC50 (concentration corresponding to 50% inhibition): dothiepin 2.8 x 10-6 M, northiaden 5.0 x 10-6 M, northiaden sulphoxide 4.0 x 10-5 M and dothiepin sulphoxide 3.2 x 10-5 M. The potencies of the drugs in inhibiting serotonergic binding followed a similar trend. Using frontal cortical tissue su..