{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:08:13Z","timestamp":1785928093547,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health on Drug Abuse","award":["DA035714"],"award-info":[{"award-number":["DA035714"]}]},{"name":"National Institutes of Health on Drug Abuse","award":["DA057866"],"award-info":[{"award-number":["DA057866"]}]},{"name":"National Institutes of Health on Drug Abuse","award":["DA047924"],"award-info":[{"award-number":["DA047924"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prolonged exposure to HIV-1 transactivator of transcription (Tat) protein dysregulates monoamine transmission, a physiological change implicated as a key factor in promoting neurocognitive disorders among people living with HIV. We have demonstrated that in vivo expression of Tat in Tat transgenic mice decreases dopamine uptake through both dopamine transporter (DAT) and norepinephrine transporter (NET) in the prefrontal cortex. Further, our novel allosteric inhibitor of monoamine transporters, SRI-32743, has been shown to attenuate Tat-inhibited dopamine transport through DAT and alleviates Tat-potentiated cognitive impairments. The current study reports the pharmacological profiles of SRI-32743 in basal and Tat-induced inhibition of human NET (hNET) function. SRI-32743 exhibited less affinity for hNET binding than desipramine, a classical NET inhibitor, but displayed similar potency for inhibiting hDAT and hNET activity. SRI-32743 concentration-dependently increased hNET affinity for [3H]DA uptake but preserved the Vmax of dopamine transport. SRI-32743 slowed the cocaine-mediated dissociation of [3H]Nisoxetine binding and reduced both [3H]DA and [3H]MPP+ efflux but did not affect d-amphetamine-mediated [3H]DA release through hNET. Finally, we determined that SRI-32743 attenuated a recombinant Tat1\u201386-induced decrease in [3H]DA uptake via hNET. Our findings demonstrated that SRI-32743 allosterically disrupts the recombinant Tat1\u201386\u2013hNET interaction, suggesting a potential treatment for HIV-infected individuals with concurrent cocaine abuse.<\/jats:p>","DOI":"10.3390\/ijms25147881","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T14:59:50Z","timestamp":1721314790000},"page":"7881","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of SRI-32743, a Novel Quinazoline Structure-Based Compound, on HIV-1 Tat and Cocaine Interaction with Norepinephrine Transporter"],"prefix":"10.3390","volume":"25","author":[{"given":"Ana Catya","family":"Jim\u00e9nez-Torres","sequence":"first","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine D.","family":"Porter","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamison A.","family":"Hastie","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8246-8560","authenticated-orcid":false,"given":"Charles","family":"Adeniran","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Moukha-Chafiq","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Scientific Platforms Division, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa H.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Scientific Platforms Division, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4791-9116","authenticated-orcid":false,"given":"Subramaniam","family":"Ananthan","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Scientific Platforms Division, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne E.","family":"Augelli-Szafran","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Scientific Platforms Division, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Guo","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA"},{"name":"Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9075-4866","authenticated-orcid":false,"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, 715 Sumter Street, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e551","DOI":"10.1212\/NXI.0000000000000551","article-title":"Antineuroinflammatory Drugs in HIV-Associated Neurocognitive Disorders as Potential Therapy","volume":"6","author":"Ambrosius","year":"2019","journal-title":"Neurol. 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