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{{Short description|Synthetic nootropic drug}} |
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| tradename = |
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| routes_of_administration = |
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<!--Identifiers--> |
<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 161417-03-4 |
| CAS_number = 161417-03-4 |
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| ATC_suffix = |
| ATC_suffix = None |
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| PubChem = 178052 |
| PubChem = 178052 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = CL2002R563 |
| UNII = CL2002R563 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 155000 |
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| C=11 | H=16 | N=2 | O=1 |
| C=11 | H=16 | N=2 | O=1 |
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| molecular_weight = 192.258 |
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| smiles = CC1=C(C=CC=N1)OC[C@@H]2CCCN2 |
| smiles = CC1=C(C=CC=N1)OC[C@@H]2CCCN2 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C11H16N2O/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10/h3,5-6,10,13H,2,4,7-8H2,1H3/t10-/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = YRVIKLBSVVNSHF-JTQLQIEISA-N |
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'''Pozanicline''' ( |
'''Pozanicline''' ([[International nonproprietary name|INN]],<ref name="INN">{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 62 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL62.pdf | publisher = World Health Organization | access-date = 3 January 2017 | page = 257 | url-status = live | archive-url = https://web.archive.org/web/20160518204538/http://www.who.int/medicines/publications/druginformation/innlists/RL62.pdf | archive-date = 18 May 2016 }}</ref> codenamed '''ABT-089''') is a drug developed by [[Abbott Laboratories|Abbott]], that has [[nootropic]] and [[neuroprotective]] effects.<ref>{{cite journal | vauthors = Lin NH, Gunn DE, Ryther KB, Garvey DS, Donnelly-Roberts DL, Decker MW, Brioni JD, Buckley MJ, Rodrigues AD, Marsh KG, Anderson DJ, Buccafusco JJ, Prendergast MA, Sullivan JP, Williams M, Arneric SP, Holladay MW | display-authors = 6 | title = Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties | journal = Journal of Medicinal Chemistry | volume = 40 | issue = 3 | pages = 385–90 | date = January 1997 | pmid = 9022806 | doi = 10.1021/jm960233u }}</ref><ref>{{cite journal | vauthors = Sullivan JP, Donnelly-Roberts D, Briggs CA, Anderson DJ, Gopalakrishnan M, Xue IC, Piattoni-Kaplan M, Molinari E, Campbell JE, McKenna DG, Gunn DE, Lin NH, Ryther KB, He Y, Holladay MW, Wonnacott S, Williams M, Arneric SP | display-authors = 6 | title = ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine]: I. A potent and selective cholinergic channel modulator with neuroprotective properties | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 283 | issue = 1 | pages = 235–46 | date = October 1997 | pmid = 9336329 }}</ref><ref>{{cite journal | vauthors = Decker MW, Bannon AW, Curzon P, Gunther KL, Brioni JD, Holladay MW, Lin NH, Li Y, Daanen JF, Buccafusco JJ, Prendergast MA, Jackson WJ, Arneric SP | display-authors = 6 | title = ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride]: II. A novel cholinergic channel modulator with effects on cognitive performance in rats and monkeys | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 283 | issue = 1 | pages = 247–58 | date = October 1997 | pmid = 9336330 }}</ref> Animal studies suggested it useful for the treatment of [[ADHD]]<ref>{{cite journal | vauthors = Prendergast MA, Jackson WJ, Terry AV, Decker MW, Arneric SP, Buccafusco JJ | title = Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys | journal = Psychopharmacology | volume = 136 | issue = 1 | pages = 50–8 | date = March 1998 | pmid = 9537682 | doi = 10.1007/s002130050538 | s2cid = 20080069 }}</ref> and subsequent human trials have shown ABT-089 to be effective for this application.<ref>{{cite journal | vauthors = Wilens TE, Verlinden MH, Adler LA, Wozniak PJ, West SA | title = ABT-089, a neuronal nicotinic receptor partial agonist, for the treatment of attention-deficit/hyperactivity disorder in adults: results of a pilot study | journal = Biological Psychiatry | volume = 59 | issue = 11 | pages = 1065–70 | date = June 2006 | pmid = 16499880 | doi = 10.1016/j.biopsych.2005.10.029 | s2cid = 24951969 }}</ref> It binds with high affinity [[nicotinic acetylcholine receptor#Subunits|subtype-selective]] to the [[Α4β2 nicotinic receptor|α<sub>4</sub>β<sub>2</sub>]] [[nicotinic acetylcholine receptors]] and has [[partial agonist|partial agonism]] to the [[α6β2|α<sub>6</sub>β<sub>2</sub>]] subtype,<ref name="pmid19481067">{{cite journal | vauthors = Marks MJ, Wageman CR, Grady SR, Gopalakrishnan M, Briggs CA | title = Selectivity of ABT-089 for alpha4beta2* and alpha6beta2* nicotinic acetylcholine receptors in brain | journal = Biochemical Pharmacology | volume = 78 | issue = 7 | pages = 795–802 | date = October 2009 | pmid = 19481067 | pmc = 2772152 | doi = 10.1016/j.bcp.2009.05.022 }}</ref><ref name="pmid19555668">{{cite journal | vauthors = Anderson DJ, Malysz J, Grønlien JH, El Kouhen R, Håkerud M, Wetterstrand C, Briggs CA, Gopalakrishnan M | display-authors = 6 | title = Stimulation of dopamine release by nicotinic acetylcholine receptor ligands in rat brain slices correlates with the profile of high, but not low, sensitivity alpha4beta2 subunit combination | journal = Biochemical Pharmacology | volume = 78 | issue = 7 | pages = 844–51 | date = October 2009 | pmid = 19555668 | doi = 10.1016/j.bcp.2009.06.024 }}</ref> but not the [[Alpha-7 nicotinic receptor|α<sub>7</sub>]] and [[Α3β4-nAChR|α<sub>3</sub>β<sub>4</sub>]] subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class.<ref>{{cite journal | vauthors = Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP | display-authors = 6 | title = ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders | journal = CNS Drug Reviews | volume = 10 | issue = 2 | pages = 167–82 | year = 2004 | pmid = 15179445 | pmc = 6741767 | doi = 10.1111/j.1527-3458.2004.tb00011.x }}</ref><ref>{{cite journal | vauthors = Wilens TE, Decker MW | title = Neuronal nicotinic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: focus on cognition | journal = Biochemical Pharmacology | volume = 74 | issue = 8 | pages = 1212–23 | date = October 2007 | pmid = 17689498 | pmc = 2974320 | doi = 10.1016/j.bcp.2007.07.002 }}</ref> |
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''Biochemical Pharmacology''. 2007 Oct 15;74(8):1212-23. PMID 17689498</ref> making it a promising candidate for clinical development. |
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==Synthesis== |
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Pozanicline is synthesized from 2-methyl-3-hydroxypyridine and Boc-L-Prolinol through a dehydration reaction followed by deprotection of the nitrogen atom of prolinol<ref>{{cite journal | vauthors = Rueter LE, Anderson DJ, Briggs CA, Donnelly-Roberts DL, Gintant GA, Gopalakrishnan M, Lin NH, Osinski MA, Reinhart GA, Buckley MJ, Martin RL, McDermott JS, Preusser LC, Seifert TR, Su Z, Cox BF, Decker MW, Sullivan JP | display-authors = 6 | title = ABT-089: pharmacological properties of a neuronal nicotinic acetylcholine receptor agonist for the potential treatment of cognitive disorders | journal = CNS Drug Reviews | volume = 10 | issue = 2 | pages = 167–82 | year = 2006 | pmid = 15179445 | pmc = 6741767 | doi = 10.1111/j.1527-3458.2004.tb00011.x | url = }}</ref> |
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== References == |
== References == |
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{{Reflist|2}} |
{{Reflist|2}} |
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{{Stimulants}} |
{{Stimulants}} |
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{{Nootropics}} |
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{{Antidementia}} |
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{{Antihyperkinetics}} |
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{{Cholinergics}} |
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{{Nicotinic acetylcholine receptor modulators}} |
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[[Category:Nicotinic agonists]] |
[[Category:Nicotinic agonists]] |
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[[Category: |
[[Category:Nootropics]] |
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[[Category:Phenol ethers]] |
[[Category:Phenol ethers]] |
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[[Category:Pyrrolidines]] |
[[Category:Pyrrolidines]] |
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