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Conversely, the affinity of this new compound at brain CCK<jats:sub>B<\/jats:sub>receptors was negligible (IC<jats:sub>50<\/jats:sub>&gt;10 \u03bc<jats:sc>M<\/jats:sc>). IQM\u201095,333 was a more selective CCK<jats:sub>A<\/jats:sub>receptor ligand than devazepide and other CCK<jats:sub>A<\/jats:sub>receptor antagonists.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Like devazepide, IQM\u201095,333 was a more potent antagonist of CCK\u20108S\u2010 than of CCK\u20104\u2010induced contraction of the longitudinal muscle from guinea\u2010pig ileum, suggesting selective antagonism at CCK<jats:sub>A<\/jats:sub>receptors.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>IQM\u201095,333 and devazepide were also potent inhibitors of CCK\u20108S\u2010stimulated amylase release from isolated pancreatic acini, a CCK<jats:sub>A<\/jats:sub>receptor\u2010mediated effect. The drug concentrations required (IC<jats:sub>50<\/jats:sub>s around 20 n<jats:sc>M<\/jats:sc>) were higher than in binding studies to pancreas homogenates.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Low doses (50\u2013100 \u03bcg kg<jats:sup>\u22121<\/jats:sup>, i.p.) of IQM\u201095,333 and devazepide, without any intrinsic effect on food intake or locomotion, blocked the hypophagia and the hypolocomotion induced by systemic administration of CCK\u20108S, two effects associated with stimulation of peripheral CCK<jats:sub>A<\/jats:sub>receptors.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>IQM\u201095,333 showed an anxiolytic\u2010like profile in the light\/dark exploration test in mice over a wide dose range (10\u20135,000 \u03bcg kg<jats:sup>\u22121<\/jats:sup>). Typical CCK<jats:sub>A<\/jats:sub>and CCK<jats:sub>B<\/jats:sub>antagonists, devazepide and L\u2010365,260 respectively, were only effective within a more limited dose range.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In a classical conflict paradigm for the study of anxiolytic drugs, the punished\u2010drinking test, IQM\u201095,333, devazepide and L\u2010365,260 were effective within a narrow dose range. The dose\u2010response curve for the three drugs was biphasic, suggesting that other mechanisms are operative at higher doses.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, IQM\u201095,333 is a potent and selective CCK<jats:sub>A<\/jats:sub>receptor antagonist both<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>with an anxiolytic\u2010like activity in two different animal models, which can only be attributed to blockade of this CCK receptor subtype.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(1997)<jats:bold>121<\/jats:bold>, 759\u2013767; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701186\">10.1038\/sj.bjp.0701186<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701186","type":"journal-article","created":{"date-parts":[[2006,8,25]],"date-time":"2006-08-25T17:10:14Z","timestamp":1156525814000},"page":"759-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Pharmacological evaluation of IQM\u201095,333, a highly selective CCK<sub>A<\/sub>receptor antagonist with anxiolytic\u2010like activity in animal models"],"prefix":"10.1111","volume":"121","author":[{"given":"Santiago","family":"Ballaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Barber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Fortu\u00f1o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn","family":"Del R\u00edo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Mart\u00edn\u2010Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"G\u00f3mez\u2010Monterrey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Herranz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosario","family":"Gonz\u00e1lez\u2010Mu\u00f1iz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u2010Teresa","family":"Garc\u00eda\u2010L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,13]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1996.tb15321.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.1991.tb00704.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245179"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(95)00081-X"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1991.01810310021005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"crossref","first-page":"11379","DOI":"10.1016\/S0021-9258(19)86497-9","article-title":"Neurotoxin binding to receptor sites associated with voltage\u2010sensitive sodium channels in intact, lysed, and detergent\u2010solubilized brain membranes","volume":"254","author":"CATTERALL W.A.","year":"1979","journal-title":"J. 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