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This compound is central nervous system (CNS) penetrant, and an oral dose of 10 mg\/kg NPY5RA-972 to rats produced concentrations in cerebrospinal fluid that Xgreatly exceeded the in vitro IC50 (inhibitory concentration 50%). Indeed, at doses to rats as low as 1 mg\/kg, NPY5RA-972 inhibited feeding induced by intracerebroventricular (ICV) administration of a selective NPY Y5 agonist ([cPP1\u20137,NPY19\u201323,Ala31,Aib32,Gln34]-hPP). However, in the dose range 1\u201310 mg\/kg, NPY5RA-972 had no significant effect on food intake in Wistar rats induced to feed by either ICV NPY or 24 h fasting or in free-feeding Wistar or obese Zucker rats. Chronic administration of NPY5RA-972 (10 mg\/kg twice daily) had no effect on food intake or body weight in either free-feeding Wistar rats or dietary obese rats. These data indicate that NPY5RA-972 is a potent, selective, orally active, and CNS-penetrant antagonist of the NPY Y5 receptor that prevents feeding driven by activation of this receptor. The data obtained with this antagonist indicate that the NPY Y5 receptor is not a major regulator of feeding in the rat.<\/jats:p>","DOI":"10.2337\/diabetes.51.8.2441","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2441-2449","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":63,"title":["Selective Antagonism of the NPY Y5 Receptor Does Not Have a Major Effect on Feeding in Rats"],"prefix":"10.2337","volume":"51","author":[{"given":"Andrew V.","family":"Turnbull","sequence":"first","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laraine","family":"Ellershaw","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave J.","family":"Masters","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Birtles","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Boyer","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie","family":"Carroll","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Clarkson","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue J.G.","family":"Loxham","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pat","family":"McAulay","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne L.","family":"Teague","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Foote","sequence":"additional","affiliation":[{"name":"From the Cardiovascular and Gastrointestinal Discovery Department, AstraZeneca, Mereside, Alderley Park, Macclesfield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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