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Concerningly,\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      has developed resistance to nearly all FDA-approved drugs. Currently, no approved oral therapies exist, with parenteral administration of ceftriaxone as the only available FDA-approved treatment option for multidrug-resistant gonococcal infections. Yet, ceftriaxone-resistant isolates have now been identified globally, further highlighting the urgent need for the development of novel antibacterial agents. In a screen of 2,528 small molecules targeting G-protein-coupled receptors and related signaling pathways, ibipinabant, a potent cannabinoid receptor 1 antagonist, was identified as having the most potent anti-gonococcal activity. Ibipinabant demonstrated potent activity against a panel of 20\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">gonorrhoeae<\/jats:italic>\n                      isolates, without inhibiting some representative\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      species of the vaginal microbiome. A time-kill assay revealed that ibipinabant is bactericidal, clearing the burden of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      (below the limit of detection) within 12 h. Ibipinabant was also able to clear the intracellular burden of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      inside human endocervical cells more effectively than the drug of choice, ceftriaxone. This drug was non-toxic against multiple cell lines and did not induce hemolysis of human red blood cells. Finally, in the\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      mouse model of\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      genital tract infection, ibipinabant showed a significant reduction (&gt;95%) in the gonococcal burden after 2 days of treatment. Altogether, these results indicate that ibipinabant is a promising candidate for drug repurposing as a novel antimicrobial against multidrug-resistant\n                      <jats:italic toggle=\"yes\">N. gonorrhoeae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01231-25","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T14:00:37Z","timestamp":1770213637000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Identification of the cannabinoid receptor 1 antagonist, ibipinabant, as a potent inhibitor of\n                    <i>Neisseria gonorrhoeae<\/i>"],"prefix":"10.1128","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9530-8267","authenticated-orcid":false,"given":"Autumn S.","family":"Dove","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]},{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for One Health Research, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2902-3551","authenticated-orcid":true,"given":"Abdallah S.","family":"Abdelsattar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]},{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for One Health Research, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader S.","family":"Abutaleb","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]},{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for One Health Research, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0939-0458","authenticated-orcid":true,"given":"Mohamed N.","family":"Seleem","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]},{"id":[{"id":"https:\/\/ror.org\/02smfhw86","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for One Health Research, Virginia Polytechnic Institute and State University","place":["Blacksburg, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"Centers for Disease Control and Prevention. 2019. 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