Manipulating neuropeptidergic pathways in humans: a novel approach to neuropharmacology?

Given the tremendous number of neuropeptides, which are synthesized in the central nervous system, the brain can be viewed as one of the most prominent endocrine organs. Elucidation of the functions of these peptides is hampered by the facts that after intravenous administration access to brain receptors is prevented or impaired by the blood-brain barrier. Here, we provide evidence that intranasal administration can be a way to circumvent the blood-brain barrier. Selected experiments will be reported indicating that peptides after intranasal administration in humans can specifically alter a great variety of brain functions. For vasopressin, we demonstrated improving effects of long-term intranasal treatment on sleep in elderly people. Insulin showed improving effects of short-term memory functions. For adrenocorticotropin/melanocyte stimulating hormone, ACTH/MSH-(4-10), a twofold action was isolated: The melanocortin fragment diminished selective attention and, with subchronic administration, reduced body fat. These results could provide the basis for developing a new, specific, and "soft" neuropharmacology. (C) 2000 Elsevier Science B.V. All rights reserved.