{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:49:08Z","timestamp":1782510548280,"version":"3.54.5"},"reference-count":21,"publisher":"Weston Medical Publishing","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Opioid Management"],"abstract":"<jats:p>Background: NLX-112 (a.k.a. F13640, befiradol) is a highly selective and fully efficacious agonist at 5-hydroxytryptamine (5-HT1A) receptors. It has been shown to be robustly and potently active in nociceptive, neuropathic and traumatic pain models in rats and mice. In particular, NLX-112 decreases oral fentanyl self-administration (FSA) in polyarthritic rats, ie, it has opioid dose-sparing effects.\r\nObjective: To examine if the dose-sparing effects of NLX-112 in polyarthritic rats are shared by other 5-HT1A ligands: the prototypical 5-HT1A receptor agonist 8-HYDROXY-2-(DI-n-PROPYLAMINO)TETRALIN ((\u00b1)8-OH-DPAT), and the 5-HT1A receptor partial agonist and weak dopamine D2 receptor blocker, buspirone.\r\nDesign: Polyarthritis was induced by inoculating rats with heat-killed Mycobacterium butyricum. They then had access to either a fentanyl (0.008 mg\/mL) or a sweetened solution in their home cage. NLX-112, (\u00b1)8-OH-DPAT, or buspirone was administered via an osmotic minipump (5 \u03bcL\/h) during a 2-week infusion period from day 14 to day 28 post-inoculation with Mycobacterium butyricum. Control infusions consisted of sterile 0.9 percent NaCl.\r\nResults: NLX-112 (0.63 mg\/day) significantly decreased FSA by 47 percent and increased total fluid consumption (TFC) by 7 percent (vehicle-loaded minipumps as controls). Both (\u00b1)8-OH-DPAT and buspirone (0.63 and 2.5 mg\/day, respectively) failed to reduce FSA; (\u00b1)8-OH-DPAT did not modify TFC, while buspirone significantly decreased it by 17 percent.\r\nConclusions: These results suggest that oral FSA dose-sparing effect, in this rat polyarthritis pain model, requires high efficacy activation of 5-HT1A receptors, such as that afforded by NLX-112. By contrast, the agonist efficacy of (\u00b1)8-OH-DPAT and buspirone seems insufficient for FSA dose-sparing.<\/jats:p>","DOI":"10.5055\/jom.0874","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T18:36:02Z","timestamp":1727289362000},"page":"269-274","source":"Crossref","is-referenced-by-count":3,"title":["Fentanyl dose-sparing in polyarthritic rats requires full agonism at 5-HT1A receptors: Comparison between NLX-112, (\u00b1)8-OH-DPAT, and buspirone"],"prefix":"10.5055","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0970-420X","authenticated-orcid":false,"given":"Ronan","family":"Depoortere","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Bardin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Newman-Tancredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3008","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"91284","doi-asserted-by":"crossref","unstructured":"Gaskin DJ, Richard P: The economic costs of pain in the United States. 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Pain. 1987; 28: 201-222.","DOI":"10.1016\/0304-3959(87)90117-5"},{"key":"91294","doi-asserted-by":"crossref","unstructured":"Bardin L, Assie MB, Pelissou M, et al.: Dual, hyperalgesic, and analgesic effects of the high-efficacy 5-hydroxytryptamine 1A (5-HT1A) agonist F13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-{[(5-methyl-pyridin-2-ylmethyl)-am ino]-methyl}piperidin-1-yl] methanone, fumaric acid salt]: Relationship with 5-HT1A receptor occupancy and kinetic parameters. J Pharmacol Exp Ther. 2005; 312: 1034-1042.","DOI":"10.1124\/jpet.104.077669"},{"key":"91295","doi-asserted-by":"crossref","unstructured":"Bardin L, Tarayre JP, Malfetes N, et al.: Profound, non-opioid analgesia produced by the high-efficacy 5-HT1A agonist F13640 in the formalin model of tonic nociceptive pain. Pharmacology. 2003; 67: 182-194.","DOI":"10.1159\/000068404"},{"key":"91296","doi-asserted-by":"crossref","unstructured":"Deseure K, Breand S, Colpaert FC: Curative-like analgesia in a neuropathic pain model: Parametric analysis of the dose and the duration of treatment with a high-efficacy 5-HT(1A) receptor agonist. Eur J Pharmacol. 2007; 568: 134-141.","DOI":"10.1016\/j.ejphar.2007.04.022"},{"key":"91297","doi-asserted-by":"crossref","unstructured":"Deseure K, Koek W, Adriaensen H, et al.: Continuous administration of the 5-hydroxytryptamine1A agonist (3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methadone (F13640) attenuates allodynia-like behavior in a rat model of trigeminal neuropathic pain. 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