{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:00:45Z","timestamp":1773010845524,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":246,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24KJ2020"],"award-info":[{"award-number":["JP24KJ2020"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advances in Pharmacological and Pharmaceutical Sciences"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    The U.S. Food and Drug Administration has approved disulfiram (DSF) as a treatment for alcoholism. DSF shows strong anxiolytic\u2010like effects in mice without the side effects commonly associated with benzodiazepines. However, when combined with alcohol, oral administration exhibits side effects, such as headache and decreased body temperature, limiting its clinical use. We aimed to evaluate the effects of intranasal DSF administration.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Male Wistar\/ST rats were used. For intranasal formulation, DSF was encapsulated by 2\u2010hydroxypropyl\u2010\u03b2\u2010cyclodextrin to form an inclusion complex. The DSF formulation exhibited a uniform particle size. The elevated plus maze (EPM) test was used to examine the anxiety\u2010reducing effects of DSF. Ethanol (2000\u2009mg\/kg, p.o.) was administered 48\u2009h after DSF. The body temperature was measured 2\u2009h after ethanol administration. Subsequently, we collected blood and measured the blood acetaldehyde levels.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Intranasal DSF administration (1.5\u2009mg\/rat) significantly increased the time spent in the open arms of the EPM within 20\u2009min of administration. Oral DSF administration of DSF (1000\u2009mg\/kg) significantly increased the time spent in the open arms of the EPM 30\u2009min after administration. In contrast to the oral administration, the intranasal DSF administration did not reduce body temperature or increase the blood acetaldehyde levels.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    The intranasal DSF administration exhibited rapid and potent anxiolytic\u2010like effects at lower doses than oral administration, without triggering the alcohol interactions observed upon oral administration. Hence, the intranasal DSF formulation may have potential clinical applications as a novel anxiolytic agent.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    Japan Registry of Clinical Trials (jRCT): jRCTs031180183\n                  <\/jats:p>","DOI":"10.1155\/adpp\/5585693","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T02:06:07Z","timestamp":1757037967000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal Administration of Disulfiram in Rats Produces Rapid and Potent Anxiolytic\u2010Like Effects Without Adverse Alcohol\u2010Related 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