biostudies-literatureKanasuwan ANational Cyclotron and PET Centre, Chulabhorn Hospital, Chulabhorn Royal Academythe National Research Council of Thailand under Molecular Probes for Imaging Research Net-work3614https://www.ebi.ac.uk/biostudies/studies/S-EPMC9959096biostudies-literatureUnknown24(4)α₃β₄ Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α₃β₄ nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, <b>(<i>S</i>)</b>-<b>QND8</b> and <b>(<i>S</i>)</b>-<b>T2</b>, for the development of an α₃β₄ nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a <i>p</i>-hydroxyl motif for ligand-recInternational journal of molecular sciencesSelective α₃β₄ Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction.PMC9959096NRCT: N10A650046N10A650046Chotipanich CArunrungvichian KVajragupta OKanasuwan ASarasamkan JDeuther-Conrad WChongruchiroj SfalseSelective α₃β₄ Nicotinic Acetylcholine Receptor Ligand as a Potential Tracer for Drug Addiction.α₃β₄ Nicotinic acetylcholine receptor (nAChR) has been recognized as an emerging biomarker for the early detection of drug addiction. Herein, α₃β₄ nAChR ligands were designed and synthesized to improve the binding affinity and selectivity of two lead compounds, <b>(<i>S</i>)</b>-<b>QND8</b> and <b>(<i>S</i>)</b>-<b>T2</b>, for the development of an α₃β₄ nAChR tracer. The structural modification was achieved by retaining the key features and expanding the molecular structure with a benzyloxy group to increase the lipophilicity for blood-brain barrier penetration and to extend the ligand-receptor interaction. The preserved key features are a fluorine atom for radiotracer development and a <i>p</i>-hydroxyl motif for ligand-rec2023-01-01T00:00:00Z2023 Feb2026-04-08T12:49:29.565Z2024-11-20T00:46:59.727ZS-EPMC99590963683502810.3390/ijms24043614