roxindole and Schizophrenia

EMD 49980 is a dopamine agonist with selective affinity to dopamine autoreceptors. Following pharmacological findings in animal studies, it was postulated that a hyperactivity of dopaminergic neurons, which is possibly present in acute schizophrenia, may be reduced by autoreceptor stimulation. To investigate the antipsychotic efficacy of EMD 49980, 20 acutely ill schizophrenics (ICD No. 295.3) were treated over four weeks with dosage increasing up to 3 mg or 9 mg. According to previously defined criteria four patients were clear responders, but clinically none of them revealed a full remission. Ten patients were nonresponders, and three of these patients were drop-outs because of marked deterioration of schizophrenic symptoms. The explorative analysis of BPRS subscales shows a statistically significant reduction of anxiety/depression and anergia, but no clear influence on the subscales THOT, HOST, and ACTV, which are the more specific scales for acute schizophrenia. EMD 49980 was subjectively well tolerated and there was no case of drug-induced extrapyramidal side-effects. In view of the only moderate antipsychotic efficacy in acute schizophrenia and the fact that antidepressant and anxiolytic effects were also observed, a clinical investigation of EMD 49980 in affective disorders and in schizophrenia with depression or anergia should be performed.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Drug Evaluation; Humans; Indoles; Middle Aged; Oxindoles; Psychiatric Status Rating Scales; Pyridines; Receptors, Dopamine; Schizophrenia; Schizophrenic Psychology

Roxindole is a potent autoreceptor-selective dopamine agonist with additional properties as a serotonin reuptake inhibitor and 5-HT1A agonist. In order to get more insight into its mode of action in various psychiatric populations, we evaluated the effects of subchronic roxindole treatment on pituitary and adrenal hormone secretion, i.e. release of prolactin, thyroid stimulating hormone (TSH), growth hormone (GH), luteinizing hormone (LH), and cortisol. Fifteen schizophrenic patients with positive and negative symptomatology, respectively, were treated with roxindole for 28 days. Both basal and thyrotropin releasing hormone (TRH) -induced prolactin secretion diminished significantly to 26.4% and 22.8% of baseline levels, respectively, under roxindole. Basal GH secretion was insignificantly elevated by 89%, whereas GH levels increased nearly 3-fold after stimulation by TRH. TSH levels decreased insignificantly to 57.5% of baseline levels, while TRH-induced TSH release was not affected by subchronic roxindole. Roxindole treatment influenced neither LH secretion nor cortisol release. Our results indicate that roxindole's dopaminergic actions might prevail over its serotonergic effects, at least as far as the regulation of anterior pituitary hormone secretion is concerned.

Topics: Adult; Dopamine Agonists; Female; Growth Hormone; Humans; Hydrocortisone; Indoles; Luteinizing Hormone; Male; Middle Aged; Oxindoles; Prolactin; Pyridines; Schizophrenia; Schizophrenic Psychology; Thyrotropin