Differential effects of the D1-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia

Abstract

In the present open study the effects of the D1-dopamine antagonist SCH 39166 on positive and negative symptoms of schizophrenia (DSM-IIIR) were investigated. SCH 39166 was given orally according to a fixed dosage schedule (day 1: 25 mg b.i.d; day 4: 50 mg b.i.d.; day 7: 100 mg b.i.d.; day 18: 200 mg b.i.d.; day 21: 225 mg b.i.d.). Seven patients completed 2 weeks, and five patients completed the study. The reason for premature withdrawal was lack of efficacy or refusal to take SCH 39166. In none of the patients a reduction of the BPRS or CGI score was found. As measured with the PANSS, a significant reduction was observed in the score of the negative subscale, whereas the positive symptoms scale and general psychopathology score remained unaffected. Akathisia, rigidity and hypokinesia were reported occasionally, although only mild in severity. The results of the present study do not support the hypothesis that D1-dopamine antagonists are clinically effective antipsychotics in schizophrenia, considering the fact that SCH 39166 had no effect on positive symptoms. The present study provides circumstantial evidence for an effect of SCH 39166 on negative symptoms.

Change of dopamine receptor mRNA expression in lymphocyte of schizophrenic patients

“…The D5 dopamine receptor, which is sparse in area of the Dl dopamine receptor, is mainly localized in the hippocampus, thalamus, and its physiological role is still uncertain [18]. However, some report suggest that the Dl dopamine receptor may be related in negative symptom [19,20] and the fact that the D5 dopamine receptor in the prefrontal cortex is down-regulated by antipsychotics in animal experiment [21] may suggest that the D5 dopamine receptor is also related to schizophrenia.…”

Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?

“…This hypothesis has been reinforced by contemporaneous imaging techniques, which have confirmed that positive symptoms were associated with an increase of dopaminergic activity in the striatum [8]. For a while, the other dopamine receptors, notably the D1 receptors, were suggested as other receptors possibly implicated in positive symptoms of schizophrenia [9], but it appeared that they were probably more involved in negative symptoms of schizophrenia, which consist of blunted effects and social withdrawal [10, 11]. D2Rs thus emerged as the primary dopaminergic modulators underlying positive symptoms [7].…”

Mechanisms of Action of Antipsychotic Drugs of Different Classes, Refractoriness to Therapeutic Effects of Classical Neuroleptics, and Individual Variation in Sensitivity to their Actions: PART I

“…It has been claimed on the basis of several clinical trials [33,34,73,74] that D1 antagonists lack antipsychotic effects. These clinical trials are not rigorous refutation of the possibility that D1 antagonists have antipsychotic effects, mainly because, in those trials, an insufficient number of patients survived a long enough test period (at least 28 days) to draw definite conclusions [102,103,App.4]).…”