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The clinical response of schizophrenic patients to treatment with gamma-type endorphins was found to be associated with certain HLA class I antigens (Bw22, B15, B13). Moreover, pretreatment of lymphocytes from healthy donors with des-Tyr1-gamma-endorphin (DT gamma E) inhibits the complement-dependent cytotoxicity between alloantisera and those HLA antigens, of which the frequency was increased among schizophrenic patients, who respond well to the gamma-endorphin therapy. Also for the opiate antagonist, naloxon interactions with HLA class I antigens could be demonstrated.

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Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo.

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A double-blind placebo-controlled cross-over investigation of the possible antipsychotic action of [des-Tyr1]-gamma-endorphin (DT gamma E) was undertaken in schizophrenic patients. This non-opiod derivative of gamma-endorphin has recently been shown to exert both neuroleptic-like effects in animals and an antipsychotic action in schizophrenic patients failing to respond to conventional neuroleptic therapy. 13 patients undergoing continuous neuroleptic therapy, and suffering from either chronic or acute, frequently-relapsing schizophrenia and displaying persistent productive symptoms (hallucinations, acute delusions) were selected for the trial.

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