{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:22:28Z","timestamp":1779366148187,"version":"3.53.0"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCN (Warsaw, Poland)","award":["2014\/15\/D\/NZ7\/01821"],"award-info":[{"award-number":["2014\/15\/D\/NZ7\/01821"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, an old drug, disulfiram, has been shown to reduce cocaine intake by inhibiting dopamine beta (\u03b2)-hydroxylase. Its effectiveness was also reported in opioid treatment, as disulfiram attenuated morphine-induced tolerance and dependence. A similar mechanism of action was evident in a selective inhibitor of D\u03b2H, nepicastat, particularly in the aspect of cocaine-seeking behavior. Hence, the objective of this study was to verify whether or not nepicastat reproduces disulfiram activity in pain reduction. Moreover, determination of its likely biological effects resulting from interactions with targets other than D\u03b2H has been given, in particular acetylcholinesterase. As was found, nepicastat was characterized by the absence of desired antinociceptive activity, though its co-administration with morphine resulted in a dose- and time-dependent enhancement of morphine-induced analgesic effect and attenuation of tolerance. Similarly, nepicastat was found to manifest antimicrobial potency against selected bacterial strains, although the effect was found to be weak. Intriguingly, this compound interacted with acetylcholinesterase through inhibition of its activity. These results clearly indicate nepicastat as a potent molecule that exhibits various biological effects. This, in turn, suggests its possible application in pathological conditions that still require effective treatment.<\/jats:p>","DOI":"10.3390\/ijms26094356","type":"journal-article","created":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T20:10:27Z","timestamp":1746389427000},"page":"4356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring Nepicastat Activity: Beyond D\u03b2H"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6659-9058","authenticated-orcid":false,"given":"Rafal","family":"Jas","sequence":"first","affiliation":[{"name":"Maria Sklodowska-Curie Medical Academy in Warsaw, 03-411 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u0142a\u017cej","family":"Grodner","sequence":"additional","affiliation":[{"name":"Chair and Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weronika","family":"Ko\u0144czak","sequence":"additional","affiliation":[{"name":"Chair and Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Fr\u0105czek","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Pharmaceutical Care, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Laskowska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Microbiology and Bioanalysis, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-9477","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Milczarek","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research, National Medicines Institute, 00-725 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Kamysz","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Pharmacy, Medical University of Gdansk, 80-416 Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-0920","authenticated-orcid":false,"given":"Patrycja","family":"Kleczkowska","sequence":"additional","affiliation":[{"name":"Maria Sklodowska-Curie Medical Academy in Warsaw, 03-411 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. 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