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Article

Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats

1
Research Unit/Neuroscience, Sohyaku, Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Yokohama 227-0033, Japan
2
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
3
Digital Transformation Department, Mitsubishi Tanabe Pharma Corporation, Tokyo 100-8205, Japan
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Yuzuru Imai, Akiyoshi Saitoh and Katsunori Nonogaki
Int. J. Mol. Sci. 2022, 23(4), 2291; https://doi.org/10.3390/ijms23042291
Received: 3 February 2022 / Revised: 17 February 2022 / Accepted: 17 February 2022 / Published: 18 February 2022
(This article belongs to the Collection State-of-the-Art Molecular Neurobiology in Japan)
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–penile 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. View Full-Text
Keywords: histamine H3 receptor; H3R; premature ejaculation; electrophysiology; in vivo extracellular recording; copulatory behavior histamine H3 receptor; H3R; premature ejaculation; electrophysiology; in vivo extracellular recording; copulatory behavior
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MDPI and ACS Style

Kiyohara, K.; Uta, D.; Nagaoka, Y.; Kino, Y.; Nonaka, H.; Ninomiya-Baba, M.; Fujita, T. Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats. Int. J. Mol. Sci. 2022, 23, 2291. https://doi.org/10.3390/ijms23042291

AMA Style

Kiyohara K, Uta D, Nagaoka Y, Kino Y, Nonaka H, Ninomiya-Baba M, Fujita T. Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats. International Journal of Molecular Sciences. 2022; 23(4):2291. https://doi.org/10.3390/ijms23042291

Chicago/Turabian Style

Kiyohara, Kazuhiro, Daisuke Uta, Yuuya Nagaoka, Yurika Kino, Hideki Nonaka, Midori Ninomiya-Baba, and Takuya Fujita. 2022. "Involvement of Histamine H3 Receptor Agonism in Premature Ejaculation Found by Studies in Rats" International Journal of Molecular Sciences 23, no. 4: 2291. https://doi.org/10.3390/ijms23042291

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