{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:48:00Z","timestamp":1791200880944,"version":"4.2.0"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,4,25]]},"abstract":"<jats:p>\n                    The biochemical and behavioral effects of a nonpeptidic, selective, and brain-penetrant agonist at the ORL1 receptor are reported herein. This low molecular weight compound {(1\n                    <jats:italic>S<\/jats:italic>\n                    ,3a\n                    <jats:italic>S<\/jats:italic>\n                    )-8- (2,3,3a,4,5,6-hexahydro-1\n                    <jats:italic>H<\/jats:italic>\n                    -phenalen-1-yl)-1-phenyl-1,3,8-triaza- spiro[4.5]decan-4-one} has high affinity for recombinant human ORL1 receptors and has 100-fold selectivity for ORL1 over other members of the opioid receptor family. It is a full agonist at these receptors and elicits dose-dependent anxiolytic-like effects in a set of validated models of distinct types of anxiety states in the rat (i.e., elevated plus-maze, fear-potentiated startle, and operant conflict). When given systemically, the compound has an efficacy and potency comparable to those of a benzodiazepine anxiolytic such as alprazolam or diazepam. However, this compound is differentiated from a classical benzodiazepine anxiolytic by a lack of efficient anti-panic-like activity, absence of anticonvulsant properties, and lack of effects on motor performance and cognitive function at anxiolytic doses (0.3 to 3 mg\/kg i.p.). No significant change in intracranial self-stimulation performance and pain reactivity was observed in this dose range. Higher doses of this compound (\u226510 mg\/kg) induced disruption in rat behavior. These data confirm the notable anxiolytic-like effects observed at low doses with the orphanin FQ\/nociceptin neuropeptide given locally into the brain and support a role for orphanin FQ\/nociceptin in adaptive behavioral fear responses to stress.\n                  <\/jats:p>","DOI":"10.1073\/pnas.090514397","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"4938-4943","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":244,"title":["A synthetic agonist at the orphanin FQ\/nociceptin receptor ORL1: Anxiolytic profile in the rat"],"prefix":"10.1073","volume":"97","author":[{"given":"Fran\u00e7ois","family":"Jenck","sequence":"first","affiliation":[{"name":"Central Nervous System Research, Roche Pharma Division, CH4070 Basel, Switzerland; and CeNes Ltd., Compass House, Vision Park, Histon, Cambridge CB4 4ZR, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Wichmann","sequence":"additional","affiliation":[{"name":"Central Nervous System Research, Roche Pharma Division, CH4070 Basel, Switzerland; 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