{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:45Z","timestamp":1787028465167,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Biphalin, one of the opioid agonists, is a dimeric analog of enkephalin with a high affinity for opioid receptors. Opioid receptors are widespread in the central nervous system and in peripheral neuronal and non-neuronal tissues. Hence, these receptors and their agonists, which play an important role in pain blocking, may also be involved in the regulation of other physiological functions. Biphalin was designed and synthesized in 1982 by Lipkowski as an analgesic peptide. Extensive further research in various laboratories on the antinociceptive effects of biphalin has shown its excellent properties. It has been demonstrated that biphalin exhibits an analgesic effect in acute, neuropathic, and chronic animal pain models, and is 1000 times more potent than morphine when administered intrathecally. In the course of the broad conducted research devoted primarily to the antinociceptive effect of this compound, it has been found that biphalin may also potentially participate in the regulation of other opioid system-dependent functions. Nearly 40 years of research on the properties of biphalin have shown that it may play a beneficial role as an antiviral, antiproliferative, anti-inflammatory, and neuroprotective agent, and may also affect many physiological functions. This integral review analyzes the literature on the multidirectional biological effects of biphalin and its potential in the treatment of many opioid system-dependent pathophysiological diseases.<\/jats:p>","DOI":"10.3390\/ijms222111347","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:22:02Z","timestamp":1634862122000},"page":"11347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biphalin\u2014A Potent Opioid Agonist\u2014As a Panacea for Opioid System-Dependent Pathophysiological Diseases?"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8654-580X","authenticated-orcid":false,"given":"Patrycja","family":"Redkiewicz","sequence":"first","affiliation":[{"name":"Department of Neuropeptides, Mossakowski Medical Research Institute Polish Academy of Sciences, 02106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1932-4019","authenticated-orcid":false,"given":"Jolanta","family":"Dyniewicz","sequence":"additional","affiliation":[{"name":"Department of Neuropeptides, Mossakowski Medical Research Institute Polish Academy of Sciences, 02106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7446-2396","authenticated-orcid":false,"given":"Aleksandra","family":"Misicka","sequence":"additional","affiliation":[{"name":"Department of Neuropeptides, Mossakowski Medical Research Institute Polish Academy of Sciences, 02106 Warsaw, Poland"},{"name":"Faculty of Chemistry, University of Warsaw, 02093 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref_1","unstructured":"Hedner, T., and Cassuto, J. 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