{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:53:19Z","timestamp":1791924799884,"version":"4.3.4"},"reference-count":72,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Riluzole, approved for amyotrophic lateral sclerosis (ALS), has a glutamate\u2010modulating profile favourable for mitigating opioid addiction. It reduces neuronal glutamate release and enhances glutamate reuptake, offering advantages over agents that only increase glutamate reuptake. However, riluzole has pharmacokinetic liabilities that limit repurposing. To overcome these limitations, we designed and prepared the prodrug troriluzole (TRLZ), which retains the mechanistic profile of riluzole but with optimized metabolic and pharmacokinetic properties (e.g., higher oral bioavailability and less pharmacokinetic variability). As dysregulation of glutamate systems during opioid exposure contributes to adverse opioid effects, we tested the hypothesis that TRLZ would inhibit several opioid\u2010derived adverse effects in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>In male Long\u2013Evans and Sprague\u2013Dawley rats, effects of TRLZ on oxycodone self\u2010administration were investigated under fixed\u2010ratio and progressive\u2010ratio reinforcement schedules. Effects of TRLZ on food self\u2010administration were also investigated. TRLZ effects on cue\u2010induced reinstatement of oxycodone seeking, and on morphine\u2010induced physical dependence, antinociceptive tolerance and respiratory depression were also investigated. TRLZ was administered intraperitoneally.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>TRLZ dose\u2010dependently reduced oxycodone self\u2010administration, reinforcing efficacy and cue\u2010induced reinstatement of oxycodone seeking without affecting inactive lever responding. TRLZ, at high doses, also inhibited food self\u2010administration. TRLZ reduced naloxone\u2010precipitated withdrawal signs in morphine\u2010dependent rats and antinociceptive tolerance during repeated morphine exposure. TRLZ also attenuated morphine\u2010induced respiratory depression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>TRLZ, already in clinical trials for cerebellar ataxia, also reduced opioid taking and seeking as well as opioid\u2010derived adverse effects in rats, supporting further study in treating opioid use disorders and pain management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70206","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T03:56:03Z","timestamp":1758686163000},"page":"505-519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Troriluzole attenuates opioid intake, reinforcing efficacy, seeking behaviours, physical dependence and antinociceptive tolerance in rats"],"prefix":"10.1111","volume":"183","author":[{"given":"Ewa","family":"Galaj","sequence":"first","affiliation":[{"name":"Psychological and Brain Sciences Colgate University  Hamilton New York USA"},{"name":"Addiction Biology Unit, National Institute on Drug Abuse Intramural Research Program  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saadet","family":"Inan","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Hua","family":"Bi","sequence":"additional","affiliation":[{"name":"Addiction Biology Unit, National Institute on Drug Abuse Intramural Research Program  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonita","family":"Wiah","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Adamson","sequence":"additional","affiliation":[{"name":"Psychological and Brain Sciences Colgate University  Hamilton New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen B.","family":"Reitz","sequence":"additional","affiliation":[{"name":"Fox Chase Therapeutics Discovery Incorporated  Doylestown Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-8104","authenticated-orcid":false,"given":"Zheng\u2010Xiong","family":"Xi","sequence":"additional","affiliation":[{"name":"Addiction Biology Unit, National Institute on Drug Abuse Intramural Research Program  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Rawls","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research, Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"},{"name":"Department of Neural Sciences, Lewis Katz School of Medicine Temple University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16177"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16182"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.16181"},{"key":"e_1_2_12_6_1","article-title":"Sex\u2010specific behavioral and thalamo\u2010accumbal circuit adaptations after oxycodone abstinence","volume":"7","author":"Alonso\u2010Caraballo 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