EEG AND CLINICAL PROFILE OF A SYNTHETIC ANALOG OF METHIONINE-ENKEPHALIN - FK-33-824

Endorphins, substances isolated from the brain and the pituitary gland, were found to have opiate-like activity via opiate receptors in the brain. Special types of brain endorphins are the enkephalins, pentapeptides which have leucin or methionine as a terminal amino acid. Methionine-enkephalin was recognized as an amino acid sequence from beta-lipotropin, a larger peptide hormone of the anterior pituitary gland. The Sandoz substance FK 33-824, a synthetically modified methionine-enkephalin, was the subject of the study. An EEG investigation of this compound in 20 normal volunteers (compared with placebo in 8 of them) indicated typical changes in electrical activity in the conventional-description and spectral-analytic evaluation, with an increase in alpha and beta activity, with a simultaneous decrease in slow waves. The changes after FK 33-824 differ from placebo changes and from the well-known changes seen after opioid alkaloids. In view of this cerebral action of FK 33-824 and of the possible involvement of endorphins in mental disease, clinical trials with the substance were initiated. In a pilot study, intramuscular FK 33-824 induced a short-term improvement in the symptoms of 4 of 6 psychotic patients. The EEG changes in normals after FK 33-824, as compared with the EEG profile after opioid substances, and the meaning of the clinical changes observed in psychotic patients will be discussed.