Since 1975, different morphinomimetic
peptides have been isolated from hypophyseal-hypothalamic extracts: the pentapeptides
methionine-enkephalin and
leucine-enkephalin, and the longer
peptides alpha-, beta- and
gamma-endorphin. The primary structure of most of these
peptides is also present in that of
beta-lipotropin. The morphinomimetic properties of
endorphins can be blocked with
opiate-antagonists. In rats, moreover, the
endorphins influence behavior which cannot be blocked with
opiate antagonists. On the basis of the hypothesis that hyperactivity of
endorphin systems may be involved in the pathogenesis of
schizophrenia and manic syndromes, the effect of
opiate antagonists on psychotic and manic symptoms has been examined in a number of clinical studies in the past few years. A transient
therapeutic effect has been demonstrated in about 30% of the patients so treated. Our own double-blind controlled study of 5 schizophrenic and 5 manic patients in the context of a World Health Organization project failed to reveal any
therapeutic effect after
subcutaneous injection of 20 mg
naloxone. The possible reasons of the negative results are discussed.