{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:15:40Z","timestamp":1791476140432,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anxiety and panic disorders are the most common mental illnesses in the United States and lack effective treatment options. Acid\u2010sending ion channels (ASICs) in the brain were shown to be associated with fear conditioning and anxiety responses and therefore are potential targets for treating panic disorder. Amiloride is an inhibitor of the ASICs in the brain and was shown to reduce panic symptoms in preclinical animal models. An intranasal formulation of amiloride will be highly beneficial to treat acute panic attacks due to advantages such as the rapid onset of action and patient compliance. The aim of this single\u2010center, open\u2010label trial was to evaluate the basic pharmacokinetics (PKs) and safety of amiloride after intranasal administration in healthy human volunteers at three doses (0.2, 0.4, and 0.6\u2009mg). Amiloride was detected in plasma within 10\u2009min of intranasal administration and showed a biphasic PK profile with an initial peak within 10\u2009min of administration followed by a second peak between 4 and 8\u2009h of administration. The biphasic PKs indicate an initial rapid absorption via the nasal pathway and later slower absorption by non\u2010nasal pathways. Intranasal amiloride exhibited a dose\u2010proportional increase in the area under the curve and did not exhibit any systemic toxicity. These data indicate that intranasal amiloride is rapidly absorbed and safe at the doses evaluated and can be further considered for clinical development as a portable, rapid, noninvasive, and nonaddictive anxiolytic agent to treat acute panic attacks.<\/jats:p>","DOI":"10.1111\/cts.13514","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T06:32:55Z","timestamp":1679121175000},"page":"1075-1084","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetics of intranasal amiloride in healthy volunteers"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-9054","authenticated-orcid":false,"given":"Venkata K.","family":"Yellepeddi","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Pediatrics University of Utah Salt Lake City Utah USA"},{"name":"Department of Molecular Pharmaceutics, College of Pharmacy University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Toronto Toronto Ontario Canada"},{"name":"Child, Youth, and Emerging Adults Programme Centre for Addiction and Mental Health Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J. 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