The vasoactive intestinal peptide (VIP) and somatostatin (somatotropin release inhibiting factor, SRIF) are important neurotransmitters in a number of basic physiological events. Their disturbances have been reported in many diseases such as cystic fibrosis, impotent man (VIP), Alzheimer's disease, and some tumours (SRIF). Xestospongine B (1), sceptrine (2), and ageliferine (3), three alkaloids isolated from Xestospongia sp. and Agelas novaecaledoniae are reported as somatostatin and VIP inhibitors. The natural products 1, 2 and 3 exhibited a high affinity for somatostatin (IC50 = 12 microM, 0.27 microM, and 2.2 microM, respectively), 2 and 3 showed an affinity for VIP (19.8 microM and 19.2 microM, respectively). Due to the interaction between non-peptidic compounds and somatostatin/VIP receptors, these three alkaloids could be promising agents in the research on natural non-peptidic compounds for therapeutical interventions.