WRYAMIDE, A NPY-BASED TRIPEPTIDE THAT ANTAGONIZES FEEDING IN RATS

Modifications of (D-Trp32) neuropeptide Y (NPY) led to the development of potential peptide-based lower molecular weight (500-800 Dal NPY fe eding antagonists. One compound, WRYamide (N-Ac-Trp-Arg-Tyr-NH2), bloc ked NPY-induced feeding for 1 to 4 h when injected intrahypothalamical ly (i.h.t.) at 1 to 40 mu g. Schedule-induced feeding was also antagon ized for up to 24 h by 20 mu g of WRYamide, i.h.t. Injection of 2.5 mg /kg (1 mg/rat) of WRYamide, i.v., also reduced significantly schedule- induced feeding for 4 h. A conditioned taste aversion could not be cla ssically conditioned to saccharin using WRYamide as the unconditioned stimulus. These results may lead to the development of systemically ac tive anti-obesity drugs. (C) 1998 Elsevier Science B.V. All rights res erved.