Academic Journal
Synthesis of α3β4 Nicotinic Acetylcholine Receptor Modulators Derived from Aristoquinoline That Reduce Reinstatement of Cocaine-Seeking Behavior
| العنوان: | Synthesis of α3β4 Nicotinic Acetylcholine Receptor Modulators Derived from Aristoquinoline That Reduce Reinstatement of Cocaine-Seeking Behavior |
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| المؤلفون: | Lisa E. Rusali, Ana M. Lopez-Hernandez, Kyle M. Kremiller, Gauri C. Kulkarni, Abhishek Gour, Carolyn J. Straub, Malaika D. Argade, Christian J. Peters, Abhisheak Sharma, Lawrence Toll, Andrea Cippitelli, Andrew P. Riley |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Biochemistry, Medicine, Neuroscience, Pharmacology, Biotechnology, Science Policy, Mental Health, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, significantly attenuates drug, promising therapeutic strategy, negative allosteric modulators, increased potency compared, primed reinstatement paradigm, prepared 22 derivatives, 1 , selective nachr inhibitor, aristoquinoline (< b, α3β4 nachr noncompetitively, reduce reinstatement, aristoquinoline derivatives, α3β4 nachr, target liabilities, several compounds, seeking behavior, possible utility, channel blockers, aristotelia chilensis, animal model, addictive properties |
| الوصف: | Growing evidence suggests that inhibition of the α3β4 nicotinic acetylcholine receptor (nAChR) represents a promising therapeutic strategy to treat cocaine use disorder. Recently, aristoquinoline ( 1 ), an alkaloid from Aristotelia chilensis, was identified as an α3β4-selective nAChR inhibitor. Here, we prepared 22 derivatives of 1 and evaluated their ability to inhibit the α3β4 nAChR. These studies revealed structure–activity trends and several compounds with increased potency compared to 1 with few off-target liabilities. Additional mechanistic studies indicated that these compounds inhibit the α3β4 nAChR noncompetitively, but do not act as channel blockers, suggesting they are negative allosteric modulators. Finally, using a cocaine-primed reinstatement paradigm, we demonstrated that 1 significantly attenuates drug-seeking behavior in an animal model of cocaine relapse. The results from these studies further support a role for the α3β4 nAChR in the addictive properties of cocaine and highlight the possible utility of aristoquinoline derivatives in treating cocaine use disorder. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://figshare.com/articles/journal_contribution/Synthesis_of_3_4_Nicotinic_Acetylcholine_Receptor_Modulators_Derived_from_Aristoquinoline_That_Reduce_Reinstatement_of_Cocaine-Seeking_Behavior/24911428 |
| DOI: | 10.1021/acs.jmedchem.3c01758.s001 |
| الاتاحة: | https://doi.org/10.1021/acs.jmedchem.3c01758.s001 https://figshare.com/articles/journal_contribution/Synthesis_of_3_4_Nicotinic_Acetylcholine_Receptor_Modulators_Derived_from_Aristoquinoline_That_Reduce_Reinstatement_of_Cocaine-Seeking_Behavior/24911428 |
| Rights: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.E5BDD885 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.3c01758.s001 |
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