gamma-endorphin--des-tyr(1)- and Psychotic-Disorders

(Des-Tyr)-gamma-endorphin is a naturally-occurring neuropeptide. It has no opiate-like activity, and animal research suggests that it shares with haloperidol certain effects on animal behaviour. The compound was given to schizophrenics, and initial claims of 'a reduction or total disappearance of symptoms in schizophrenics partly or completely resistant to conventional neuroleptics and suffering from long-lasting psychoses' were made. Several investigators have attempted to replicate these findings without success. This paper reviews the shortcomings in methodology and interpretation of results of the investigations carried out so far and emphasises that the fundamental question of whether (Des-Tyr)-gamma-endorphin has any clinical antipsychotic effect has not been answered by any study to date.

Topics: Antipsychotic Agents; Endorphins; Humans; Peptide Fragments; Psychotic Disorders; Schizophrenia

The pharmacological actions of gamma-type endorphins show similarities to those of the neuroleptics. Two fragments of gamma-endorphin (beta-LPH 61-77) were therefore tested in patients with schizophrenic and schizo-affective psychoses who had shown an insufficient response to neuroleptics. The fragments were DT gamma E (beta-LPH 62-77) and DE gamma E (beta-LPH 66-77). Some of the patients studied responded favorably to this treatment. A number of criteria of differentiation between responders and nonresponders are discussed. The influence of DT gamma E on the central DA metabolism differs from that of the neuroleptics. It is therefore conceivable that gamma-type endorphins represent a different principle of action. The therapeutic efficacy of these compounds lends support to the hypothesis that disorders of central endorphin metabolism may play a role in the pathogenesis of psychoses of the schizophrenic type.

Topics: beta-Endorphin; Brain; Clinical Trials as Topic; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychotic Disorders; Receptors, Dopamine; Schizophrenia; Schizophrenic Psychology

Topics: Brief Psychiatric Rating Scale; Double-Blind Method; Drug Evaluation; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychotic Disorders; Schizophrenia

The neuropeptide (des-tyrosine1)-gamma-endorphin (DT gamma E; beta-LPH 62-77) was given to 10 schizophrenic patients who had been free of neuroleptic medication for at least 3 weeks. DT gamma E was injected intramuscularly in a dose of 1 mg daily for 10 days following a double-blind placebo-controlled crossover design. In 4 of the 10 patients a pronounced antipsychotic effect was observed; in 3 a temporary or slight reduction of psychotic symptoms occurred; and in 3 no response was noted. DT gamma E led to decreased plasma levels of prolactin and in some patients to increased concentrations of homovanillic acid in cerebrospinal fluid (CSF). Neither plasma levels of growth hormone and cortisol nor CSF concentrations of 5-hydroxyindoleacetic acid were affected by DT gamma E. These data confirm that DT gamma E has antipsychotic properties in a number of schizophrenic patients and suggest an interaction between DT gamma E and central dopaminergic systems.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Endorphins; Female; Growth Hormone; Humans; Hydrocortisone; Male; Peptide Fragments; Prolactin; Psychotic Disorders; Schizophrenia; Schizophrenia, Catatonic; Schizophrenia, Paranoid; Schizophrenic Psychology

Topics: Animals; Antipsychotic Agents; Behavior, Animal; beta-Endorphin; Dopamine; Double-Blind Method; Endorphins; gamma-Endorphin; Humans; Peptide Fragments; Psychiatric Status Rating Scales; Psychotic Disorders; Rats; Receptors, Dopamine; Receptors, Opioid; Schizophrenia; Schizophrenic Psychology