{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:27:06Z","timestamp":1785803226040,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science KAKENHI","award":["JP19K09323, JP15K08667, JP25860431, and JP21600005"],"award-info":[{"award-number":["JP19K09323, JP15K08667, JP25860431, and JP21600005"]}]},{"DOI":"10.13039\/501100012351","name":"Mitsubishi Tanabe Pharma Corporation","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/501100012351","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Adaptable and Seamless Technology Transfer Program through Target-driven R&amp;D from the Japan Science and Technology Agency","award":["JPMJTM20DN"],"award-info":[{"award-number":["JPMJTM20DN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several of the drugs currently available for the treatment of premature ejaculation (PE) (e.g., local anesthetics or antidepressants) are associated with numerous safety concerns and exhibit weak efficacy. To date, no therapeutics for PE have been approved in the United States, highlighting the need to develop novel agents with sufficient efficacy and fewer side effects. In this study, we focused on the histamine H3 receptor (H3R) as a potential target for the treatment of PE and evaluated the effects of imetit (an H3R\/H4R agonist), ciproxifan (an H3R antagonist), and JNJ-7777120 (an H4R antagonist) in vivo. Our in vivo electrophysiological experiments revealed that imetit reduced mechanical stimuli-evoked neuronal firing in anesthetized rats. This effect was inhibited by ciproxifan but not by JNJ-7777120. Subsequently, we evaluated the effect of imetit using a copulatory behavior test to assess ejaculation latency (EL) in rats. Imetit prolonged EL, although this effect was inhibited by ciproxifan. These findings indicate that H3R stimulation suppresses mechanical stimuli-evoked neuronal firing in the spinal\u2013penile neurotransmission system, thereby resulting in prolonged EL. To our knowledge, this is the first report to describe the relationship between H3R and PE. Thus, H3R agonists may represent a novel treatment option for PE.<\/jats:p>","DOI":"10.3390\/ijms23042291","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T09:18:42Z","timestamp":1645435122000},"page":"2291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-7046","authenticated-orcid":false,"given":"Kazuhiro","family":"Kiyohara","sequence":"first","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5644-1348","authenticated-orcid":false,"given":"Daisuke","family":"Uta","sequence":"additional","affiliation":[{"name":"Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuya","family":"Nagaoka","sequence":"additional","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurika","family":"Kino","sequence":"additional","affiliation":[{"name":"Digital Transformation Department, Mitsubishi Tanabe Pharma Corporation, Tokyo 100-8205, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Nonaka","sequence":"additional","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Ninomiya-Baba","sequence":"additional","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Fujita","sequence":"additional","affiliation":[{"name":"Research Unit\/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","unstructured":"(2021, December 01). 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