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 Da) NPY feeding antagonists. One compound, WRYamide (N-Ac-Trp-Arg-Tyr-NH2), blocked NPY-induced feeding for 1 to 4 h when injected intrahypothalamically (i.h.t.) at 1 to 40 microgram. Schedule-induced feeding was also antagonized for up to 24 h by 20 microgram 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 classically conditioned to saccharin using WRYamide as the unconditioned stimulus. These results may lead to the development of systemically active anti-obesity drugs.
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Department of Surgery, University of Cincinnati Medical Center, 231 Bethesda Avenue, Cincinnati, OH 45267, USA.
Tao
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Sheriff
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Balasubramaniam
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D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012439:Saccharin / Q000494:pharmacology; D013997:Time Factors
D001067:Appetite Depressants; D009478:Neuropeptide Y; D009842:Oligopeptides; C118952:WRYamide; D012439:Saccharin