raclopride and Acute-Disease

Response to typical antipsychotic medication has been associated with achieving a level of striatal dopamine D2 receptor occupancy in the range of 65% to 70%. We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy.. Eighteen patients who presented with a first episode of psychosis were randomized to receive olanzapine 5 mg daily or haloperidol 2 mg daily in a double-blind design. We acquired positron emission tomography (PET) scans using the D2 ligand [11C]raclopride within the first 15 days of treatment to determine the percentage of D2 receptors occupied by the medication. According to response, dosage was then adjusted to a maximum dosage of 20 mg daily of either drug. PET scans were repeated after 10 to 12 weeks of treatment.. At the first PET scan, the 8 olanzapine-treated patients had significantly lower D2 receptor occupancies (mean 63.4%, SD 7.3) than those observed in the 10 patients treated with haloperidol (mean 73.0%, SD 6.1). When patients were rescanned following dosage adjustment, mean D2 receptor occupancies were greater than 70% in both groups. D2 receptor occupancies did not differ significantly between the olanzapine-treated group (mean 72.0%, SD 5.7) and the haloperidol-treated group (mean 78.7%, SD 7.6).. These results suggest that, in patients being treated for a first episode of psychosis, olanzapine has its antipsychotic effect at approximately the same levels of D2 receptor occupancy as are achieved with low dosages of haloperidol.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Corpus Striatum; Dose-Response Relationship, Drug; Double-Blind Method; Female; Haloperidol; Humans; Male; Olanzapine; Positron-Emission Tomography; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

The effect of the selective serotonin-2 antagonist ritanserin was investigated in an open study of patients with schizophrenia. The patients were in an acute psychotic state considered to require neuroleptic medication. No neuroleptic drug was allowed during the study or during the last month preceeding the study. Oxazepam or nitrazepam were allowed for sedation or sleep inducement. Safety, tolerability, potential antipsychotic effect, and drug effects on monoamine metabolites in serum and CSF and prolactin in serum were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography. Ten male patients (mean age 32.4) fulfilling DSM-III-R criteria for schizophrenia were included in the study. Nine of these patients completed 4 weeks' treatment with ritanserin 10 mg b.i.d. The clinical effect was evaluated by means of CPRS and SANS and significant improvement was seen after 4 weeks' treatment both in positive and negative symptoms. Ritanserin was well tolerated and no extrapyramidal symptoms or akathisia were seen. Concentrations of monoamine metabolites and prolactin did not change during treatment. Ritanserin did not occupy D2-dopamine receptors. Thus, no indications of any D2-dopamine-antagonistic activity were obtained. All patients had expected ritanserin levels in plasma during the whole study. This first study of a selective serotonin-2 antagonist in the treatment of acute schizophrenic patients demonstrated significant clinical effects. However, the open design of the study does not allow us to conclude with any certainty that the patients' improvement was due to a specific blockade of serotonin-2 receptors or unspecific factors, although a direct D2-dopamine blockade could be ruled out.

Topics: Acute Disease; Adult; Antipsychotic Agents; Biogenic Monoamines; Hemodynamics; Humans; Male; Prolactin; Psychiatric Status Rating Scales; Raclopride; Receptors, Dopamine D2; Ritanserin; Salicylamides; Schizophrenia; Schizophrenic Psychology; Serotonin; Tomography, Emission-Computed

Fifteen acutely ill patients (8 male, 7 female) aged 19 to 63 who met DSM-III criteria for schizophrenic disorder or schizophreniform disorder participated in a 4-week open trial of raclopride. The starting dose of raclopride was 2 mg increasing to 4 mg twice daily in the first week, further increments to 6 mg twice daily at day 14, and 8 mg twice daily at day 21 depending on response. Weekly assessments were made using the BPRS, Montgomery Schizophrenia Scale, Krawiecka-Goldberg Scale and Clinical Global Impression Scale. Extra-pyramidal symptoms and other side-effects were recorded weekly. Four patients failed to complete. Two were withdrawn because of clinical deterioration, and 2 others left hospital against advice after 2 weeks having shown initial improvement. Of the 11 completers, 4 were very much improved and 6 much improved; one was minimally worse. Extra-pyramidal symptoms were infrequent: 3 patients expressed occasional mild akathisia. Six patients complained of mild drowsiness. No major deviations were found in biochemical and physiological safety parameters. Plasma concentrations of raclopride were stable throughout treatment or proportional to dose changes. There was approximately a 6-fold inter-individual difference in steady-state drug concentrations. Plasma levels of prolactin increased transiently after raclopride intake to a maximum of up to 80 and 130 ng/ml in male and female patients respectively.

Topics: Acute Disease; Adult; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Raclopride; Receptors, Dopamine; Receptors, Dopamine D2; Salicylamides; Schizophrenia; Schizophrenic Psychology

Raclopride, a highly selective D2-dopamine receptor antagonist, was administered in doses up to 4 mg b.i.d. to ten schizophrenic patients in an open label non-comparative study lasting 4 weeks. Safety, tolerability, potential antipsychotic effect, prolactin response and drug effect on plasma homovanillic acid were evaluated. Central D2-dopamine receptor occupancy was determined by positron emission tomography (PET). No major deviations were found in biochemical and physiological safety parameters. Raclopride was well tolerated. The mean BPRS score was reduced by 55% at endpoint. In the global evaluation seven patients were "very much" or "much" improved. Extrapyramidal side effects were recorded in four patients and disappeared after dose reduction or single doses of biperiden. An increase in plasma prolactin of short duration was observed in both sexes. A significant decrease of plasma HVA was obtained after 4 weeks of treatment. In two of the patients the central D2-dopamine receptors occupancy was measured using PET. The receptor occupancy was 68 and 72% which is the same as that found in patients treated with conventional neuroleptics.

Topics: Acute Disease; Adolescent; Adult; Female; Hemodynamics; Homovanillic Acid; Humans; Male; Middle Aged; Prolactin; Raclopride; Receptors, Dopamine; Salicylamides; Schizophrenia; Tomography, Emission-Computed

Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Acute Disease; Animals; Benzazepines; Biperiden; Cebus; Drug Interactions; Dyskinesia, Drug-Induced; Ergolines; Male; Quinpirole; Raclopride; Receptors, Dopamine; Salicylamides