The anorectic and dipsogenic effects of the pancreatic hormone amylin are mediated by the area postrema and the subfornical organ. We tested the effectiveness of a new amylin antagonist, a so-called RNA Spiegelmer, by electrophysiological in-vitro recordings from the rat subfornical organ and by immunohistological c-Fos studies in the area postrema. Amylin's excitatory effect on subfornical organ neurons was blocked by the anti-amylin Spiegelmer. Peripheral administration 5 h prior to amylin also suppressed the amylin-induced activation (c-Fos expression) in the area postrema. The biostable anti-amylin Spiegelmer may be therapeutically beneficial in conditions associated with high plasma amylin levels, such as cancer anorexia occurring during certain pancreatic tumors.