Dopamine autoreceptor agonists reduce the firing rate, synthesis, and release of
dopamine in dopaminergic neurons by means of a negative feedback mechanism via stimulation of
autoreceptors. Moreover,
dopamine autoreceptor agonists are able to stimulate supersensitive but not normosensitive postsynaptic receptors. For
dopamine autoreceptor agonists,
therapeutic effects by readjustment of excessive or deficient dopaminergic function have been postulated for positive and negative schizophrenic symptomatology as well as for subtypes of
depressive disorders. Investigations on the
therapeutic effects of
autoreceptor-nonselective
dopamine agonists in
schizophrenia or depression have yielded inconsistent results. In order to reduce the excess of central dopaminergic activity postulated by the
dopamine hypothesis of
schizophrenia,
dopamine autoreceptor agonists have been tested in open clinical trials in positive schizophrenic symptomatology. However, administration of selective
dopamine autoreceptor agonists like
talipexole or
roxindole did not result in a significant improvement of positive psychotic symptoms. In negative schizophrenic symptomatology, a
dopamine deficit rather than an excess has been hypothesized. Current evidence from pilot studies suggests that
dopamine autoreceptor agonists like
roxindole may produce a minor to moderate improvement of symptoms like affective flattening, depressed mood,
alogia, and avolition, possibly by stimulation of supersensitive postsynaptic
dopamine receptors. For certain subgroups of depression, a reduction of functional
dopamine activity has been postulated. In an open pilot study in patients with a major depression,
roxindole demonstrated antidepressive properties comparable to those of standard
antidepressants, justifying further double-blind controlled trials against reference drugs.