Dopamine agonists in schizophrenia: a review.
Although it is unlikely that the different types of course and severity of schizophrenia are caused by one neurochemical abnormality alone, indirect pharmacological evidence still suggests a relative excess of dopaminergic activity being implicated in the pathogenesis of most of the schizophrenic symptoms, e.g. positive symptomatology. Synthesis and release of dopamine as well as firing rates of dopaminergic neurons are controlled by stimulation of autoreceptors via a negative feedback regulation. Investigations on therapeutic effects of autoreceptor-nonselective dopamine agonists in schizophrenia have yielded inconsistent results. Dopamine autoreceptor agonists like pramipexole, roxindole, talipexole and OPC-4392 as well as partial agonists like terguride and SDZ HDC 912 have been tested in positive schizophrenic symptomatology in order to reduce the postulated excess of central dopaminergic activity. However, administration of autoreceptor-'selective' agonists did not result in a significant improvement of positive symptoms. In predominantly negative schizophrenic symptomatology, a dopamine deficit rather than an excess has been hypothesized. Consequently, a nonselective dopamine agonistic action could be effective in some negative symptoms. Current evidence from several open and one placebo-controlled clinical trial suggests that some dopamine autoreceptor agonists like pramipexole, roxindole and talipexole may produce a mild improvement of symptoms like affective flattening, depressed mood, alogia and avolition. Nevertheless, these findings do not yet allow a reliable judgement and remain to be clarified by further double-blind placebo-controlled studies over a sufficient treatment duration.
Benkert
O
O
Department of Psychiatry, University of Mainz, Germany.
Müller-Siecheneder
F
F
Wetzel
H
H
D014150:Antipsychotic Agents / Q000627:therapeutic use; D017660:Autoreceptors / Q000187:drug effects; D001381:Azepines / Q000627:therapeutic use; D052160:Benzothiazoles; D018491:Dopamine Agonists / Q000627:therapeutic use*; D006801:Humans; D000077487:Pramipexole; D012559:Schizophrenia / Q000188:drug therapy*; D013844:Thiazoles / Q000627:therapeutic use
D014150:Antipsychotic Agents; D017660:Autoreceptors; D001381:Azepines; D052160:Benzothiazoles; D018491:Dopamine Agonists; D013844:Thiazoles; C024763:talipexole; D000077487:Pramipexole