{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:55:41Z","timestamp":1789052141154,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":455,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Rimonabant (Acomplia<jats:sup>TM<\/jats:sup>, SR141716A), a cannabinoid CB<jats:sub>1<\/jats:sub> receptor inverse agonist, has recently been approved for the treatment of obesity. There are, however, concerns regarding its side effect profile. Developing a CB<jats:sub>1<\/jats:sub> antagonist with a different pharmacological mechanism may lead to a safer alternative. To this end we have screened a proprietary small molecule library and have discovered a novel class of allosteric antagonist at CB<jats:sub>1<\/jats:sub> receptors. Herein, we have characterized an optimized prototypical molecule, PSNCBAM\u20101, and its hypophagic effects <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>A CB<jats:sub>1<\/jats:sub> yeast reporter assay was used as a primary screen. PSNCBAM\u20101 was additionally characterized in [<jats:sup>35<\/jats:sup>S]\u2010GTP\u03b3S, cAMP and radioligand binding assays. An acute rat feeding model was used to evaluate its effects on food intake and body weight <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>In CB<jats:sub>1<\/jats:sub> receptor yeast reporter assays, PSNCBAM\u20101 blocked the effects induced by agonists such as CP55,940, WIN55212\u20102, anandamide (AEA) or 2\u2010arachidonoyl glycerol (2\u2010AG). The antagonist characteristics of PSNCBAM\u20101 were confirmed in [<jats:sup>35<\/jats:sup>S]\u2010GTP\u03b3S binding and cAMP assays and was shown to be non\u2010competitive by Schild analyses. PSNCBAM\u20101 did not affect CB<jats:sub>2<\/jats:sub> receptors. In radioligand binding assays, PSNCBAM\u20101 increased the binding of [<jats:sup>3<\/jats:sup>H]CP55,940 despite its antagonist effects. In an acute rat feeding model, PSNCBAM\u20101 decreased food intake and body weight.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>PSNCBAM\u20101 exerted its effects through selective allosteric modulation of the CB<jats:sub>1<\/jats:sub> receptor. The acute effects on food intake and body weight induced in rats provide a first report of <jats:italic>in vivo<\/jats:italic> activity for an allosteric CB<jats:sub>1<\/jats:sub> receptor antagonist.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>152<\/jats:bold>, 805\u2013814; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707347\">10.1038\/sj.bjp.0707347<\/jats:ext-link>; published online 25 June 2007<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707347","type":"journal-article","created":{"date-parts":[[2007,6,25]],"date-time":"2007-06-25T12:09:57Z","timestamp":1182773397000},"page":"805-814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":170,"title":["PSNCBAM\u20101, a novel allosteric antagonist at cannabinoid CB<sub>1<\/sub> receptors with hypophagic effects in rats"],"prefix":"10.1111","volume":"152","author":[{"given":"J G","family":"Horswill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Bali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Shaaban","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Keily","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Jeevaratnam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Babbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Reynet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Wong Kai 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