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{{Short description|Chemical compound}}{{Drugbox
{{Drugbox
| Verifiedfields = changed
⚫ | verifiedrevid = 444000503
| Watchedfields = changed
⚫ | IUPAC_name = 5-( methoxy)- 2-chloropyridine
⚫ | verifiedrevid = 448113374
⚫ | image = Tebaniciclina.png
⚫ | IUPAC_name = 5-{methoxy}-2-chloropyridine
| width = 240
⚫ | image = Tebanicline.svg


<!--Clinical data--> <!--Clinical data-->
| tradename = | tradename =
| routes_of_administration = | routes_of_administration =


<!--Identifiers--> <!--Identifiers-->
| IUPHAR_ligand = 3989
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 198283-73-7 | CAS_number = 198283-73-7
| ATC_prefix = none | ATC_prefix = none
| ATC_suffix = | ATC_suffix =
| PubChem = 3075702 | PubChem = 3075702
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 430497
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 9KX8NKV538 | UNII = 9KX8NKV538
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 2334347
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C9H11ClN2O/c10-9-2-1-8(5-12-9)13-6-7-3-4-11-7/h1-2,5,7,11H,3-4,6H2/t7-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = MKTAGSRKQIGEBH-SSDOTTSWSA-N


<!--Chemical data--> <!--Chemical data-->
| C=9 | H=11 | Cl=1 | N=2 | O=1 | C=9 | H=11 | Cl=1 | N=2 | O=1
| molecular_weight = 198.649 | molecular_weight =
| smiles = C1CN1COC2=CN=C(C=C2)Cl | smiles = C1CN1COC2=CN=C(C=C2)Cl
}} }}


'''Tebanicline''' ('''ebanicline''', '''ABT-594''') is a potent synthetic nicotinic (non-opioid) analgesic drug developed by ]. It was developed as a less toxic ] of the potent ]-derived compound ], which is about 200 times stronger than ] as an ], but produces extremely dangerous toxic side effects.<ref>{{cite journal | vauthors = Bannon AW, Decker MW, Holladay MW, Curzon P, Donnelly-Roberts D, Puttfarcken PS, Bitner RS, Diaz A, Dickenson AH, Porsolt RD, Williams M, Arneric SP | display-authors = 6 | title = Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors | journal = Science | volume = 279 | issue = 5347 | pages = 77–81 | date = January 1998 | pmid = 9417028 | doi = 10.1126/science.279.5347.77 | bibcode = 1998Sci...279...77B }}</ref><ref>{{cite journal | vauthors = Holladay MW, Wasicak JT, Lin NH, He Y, Ryther KB, Bannon AW, Buckley MJ, Kim DJ, Decker MW, Anderson DJ, Campbell JE, Kuntzweiler TA, Donnelly-Roberts DL, Piattoni-Kaplan M, Briggs CA, Williams M, Arneric SP | display-authors = 6 | title = Identification and initial structure-activity relationships of (R)-5-(2-azetidinylmethoxy)-2-chloropyridine (ABT-594), a potent, orally active, non-opiate analgesic agent acting via neuronal nicotinic acetylcholine receptors | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 4 | pages = 407–12 | date = February 1998 | pmid = 9484491 | doi = 10.1021/jm9706224 }}</ref> Like epibatidine, tebanicline showed potent analgesic activity against ] in both animal and human trials, but with far less toxicity than its parent compound.<ref>{{cite journal | vauthors = Donnelly-Roberts DL, Puttfarcken PS, Kuntzweiler TA, Briggs CA, Anderson DJ, Campbell JE, Piattoni-Kaplan M, McKenna DG, Wasicak JT, Holladay MW, Williams M, Arneric SP | display-authors = 6 | title = ABT-594 : a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 285 | issue = 2 | pages = 777–86 | date = May 1998 | pmid = 9580626 | url = http://jpet.aspetjournals.org/content/285/2/777.long }}</ref><ref>{{cite journal | vauthors = Bannon AW, Decker MW, Curzon P, Buckley MJ, Kim DJ, Radek RJ, Lynch JK, Wasicak JT, Lin NH, Arnold WH, Holladay MW, Williams M, Arneric SP | display-authors = 6 | title = ABT-594 : a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 285 | issue = 2 | pages = 787–94 | date = May 1998 | pmid = 9580627 | url = http://jpet.aspetjournals.org/content/285/2/787.long }}</ref><ref>{{cite journal | vauthors = Decker MW, Bannon AW, Buckley MJ, Kim DJ, Holladay MW, Ryther KB, Lin NH, Wasicak JT, Williams M, Arneric SP | display-authors = 6 | title = Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice | journal = European Journal of Pharmacology | volume = 346 | issue = 1 | pages = 23–33 | date = April 1998 | pmid = 9617748 | doi = 10.1016/S0014-2999(98)00042-9 }}</ref><ref>{{cite journal | vauthors = Kesingland AC, Gentry CT, Panesar MS, Bowes MA, Vernier JM, Cube R, Walker K, Urban L | display-authors = 6 | title = Analgesic profile of the nicotinic acetylcholine receptor agonists, (+)-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain | journal = Pain | volume = 86 | issue = 1–2 | pages = 113–8 | date = May 2000 | pmid = 10779668 | doi = 10.1016/s0304-3959(00)00233-5 | s2cid = 26170267 }}</ref><ref>{{cite journal| vauthors = Sorbera LA, Revel L, Leeson P, Castaner J |title=ABT-594|journal=Drugs of the Future|volume=26|issue=10|pages=927|doi=10.1358/dof.2001.026.10.640317|year=2001}}</ref><ref>{{cite journal | vauthors = Lynch JJ, Wade CL, Mikusa JP, Decker MW, Honore P | title = ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model | journal = European Journal of Pharmacology | volume = 509 | issue = 1 | pages = 43–8 | date = February 2005 | pmid = 15713428 | doi = 10.1016/j.ejphar.2004.12.034 }}</ref> It acts as a ] at neuronal ]s, binding to both the ] and the ] ].<ref>{{cite journal | vauthors = Jain KK | title = Modulators of nicotinic acetylcholine receptors as analgesics | journal = Current Opinion in Investigational Drugs | volume = 5 | issue = 1 | pages = 76–81 | date = January 2004 | pmid = 14983978 }}</ref>
'''Tebanicline''' ('''Ebanicline''', '''ABT-594''') is a drug developed by ], which acts as a ] at neuronal ]s, binding to both the ] and the ] ].<ref>{{Cite pmid|14983978}}</ref> It was developed as a less toxic analogue of the potent frog-derived compound ], which is some 200x stronger than ] as an ] but produces extremely dangerous toxic side effects.<ref>{{Cite pmid|9417028}}</ref><ref>{{Cite pmid|9484491}}</ref> Like epibatidine, tebanicline showed potent analgesic activity against ] in both animal and human trials, but with far less toxicity than its parent compound.<ref>{{Cite pmid|9580626}}</ref><ref>{{Cite pmid|9580627}}</ref><ref>{{Cite pmid|9617748}}</ref><ref>{{Cite pmid|10779668}}</ref><ref>Sorbera LA, Revel L, Leeson PA, Castaner J. ABT-594. ''Drugs Future'' 2001; 26: 927-934).</ref><ref>{{Cite pmid|15713428}}</ref>


Tebanicline progressed to Phase II clinical trials in humans,<ref>{{cite journal | vauthors = Decker MW, Meyer MD, Sullivan JP | title = The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control | journal = Expert Opinion on Investigational Drugs | volume = 10 | issue = 10 | pages = 1819–30 | date = October 2001 | pmid = 11772288 | doi = 10.1517/13543784.10.10.1819 | s2cid = 24924290 }}</ref> but was dropped from further development due to unacceptable incidence of ] side effects.<ref>{{cite journal| vauthors = Meyer MD |title=Neuronal nicotinic acetylcholine receptors as a target for the treatment of neuropathic pain|journal=Drug Development Research|date=1 April 2006|issn=1098-2299|pages=355–359|volume=67|issue=4|doi=10.1002/ddr.20099|s2cid=84222640}}</ref> However, further research in this area is ongoing,<ref>{{cite journal | vauthors = Baraznenok IL, Jonsson E, Claesson A | title = 3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: synthesis and analgesic activity | journal = Bioorganic & Medicinal Chemistry Letters | volume = 15 | issue = 6 | pages = 1637–40 | date = March 2005 | pmid = 15745813 | doi = 10.1016/j.bmcl.2005.01.058 }}</ref><ref>{{cite journal | vauthors = Zhang CX, Ge ZM, Cheng TM, Li RT | title = Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594 | journal = Bioorganic & Medicinal Chemistry Letters | volume = 16 | issue = 7 | pages = 2013–6 | date = April 2006 | pmid = 16412637 | doi = 10.1016/j.bmcl.2005.12.073 }}</ref><ref>{{cite journal | vauthors = Bunnelle WH, Daanen JF, Ryther KB, Schrimpf MR, Dart MJ, Gelain A, Meyer MD, Frost JM, Anderson DJ, Buckley M, Curzon P, Cao YJ, Puttfarcken P, Searle X, Ji J, Putman CB, Surowy C, Toma L, Barlocco D | display-authors = 6 | title = Structure-activity studies and analgesic efficacy of N-(3-pyridinyl)-bridged bicyclic diamines, exceptionally potent agonists at nicotinic acetylcholine receptors | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 15 | pages = 3627–44 | date = July 2007 | pmid = 17585748 | doi = 10.1021/jm070018l }}</ref><ref>{{cite journal | vauthors = Joshi SK, Mikusa JP, Weaver B, Honore P | title = Morphine and ABT-594 (a nicotinic acetylcholine agonist) exert centrally mediated antinociception in the rat cyclophosphamide cystitis model of visceral pain | journal = The Journal of Pain | volume = 9 | issue = 2 | pages = 146–56 | date = February 2008 | pmid = 18088559 | doi = 10.1016/j.jpain.2007.09.004 | doi-access = free }}</ref> and the development of nicotinic acetylcholine receptor agonists is ongoing.<ref>{{cite journal | vauthors = Lloyd GK, Williams M | year = 2000 | title = Neuronal Nicotinic Acetylcholine Receptors as Novel Drug Targets | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 292 | issue = 2| pages = 461–467 | pmid = 10640281 }}</ref><ref>{{cite journal | vauthors = Vincler M | title = Neuronal nicotinic receptors as targets for novel analgesics | journal = Expert Opinion on Investigational Drugs | volume = 14 | issue = 10 | pages = 1191–8 | date = October 2005 | pmid = 16185161 | doi = 10.1517/13543784.14.10.1191 | s2cid = 20618128 }}</ref><ref>{{cite journal | vauthors = Arneric SP, Holladay M, Williams M | title = Neuronal nicotinic receptors: a perspective on two decades of drug discovery research | journal = Biochemical Pharmacology | volume = 74 | issue = 8 | pages = 1092–101 | date = October 2007 | pmid = 17662959 | doi = 10.1016/j.bcp.2007.06.033 | series = Nicotinic Acetylcholine Receptors as Therapeutic Targets: Emerging Frontiers in Basic Research and Clinical Science }}</ref><ref>{{cite journal | vauthors = Wells GB | title = Structural answers and persistent questions about how nicotinic receptors work | journal = Frontiers in Bioscience | volume = 13 | issue = 13 | pages = 5479–510 | date = May 2008 | pmid = 18508600 | pmc = 2430769 | doi = 10.2741/3094 }}</ref> No agents from this class have successfully completed human clinical trials due to their unacceptable side effect profiles. Research in the area continues.<ref>{{cite journal | vauthors = Umana IC, Daniele CA, McGehee DS | date = Oct 2013 | title = Neuronal nicotinic receptors as analgesic targets: it's a winding road | journal = Biochem Pharmacol | volume = 86 | issue = 8| pages = 1208–14 | doi = 10.1016/j.bcp.2013.08.001 | pmid = 23948066 | pmc = 4127197 }}</ref>
Tebanicline got as far as Phase II trials in humans,<ref>{{Cite pmid|11772288}}</ref> but was dropped from further development due to unacceptable incidence of gastrointestinal side effects.<ref>Meyer MD. Neuronal Nicotinic Acetylcholine Receptors as a Target for the Treatment of Neuropathic Pain. ''Drug Development Research''. 2006; 67: 355-359.</ref> However further research in this area is ongoing,<ref>{{Cite pmid|15745813}}</ref><ref>{{Cite pmid|16412637}}</ref><ref>{{Cite pmid|17585748}}</ref><ref>{{Cite pmid|18088559}}</ref> and it is expected that development of new neural nicotinic acetylcholine receptor agonists will be likely to lead to novel analgesics suitable for use in humans within the next few years.<ref>Lloyd GK, Williams M. Neuronal Nicotinic Acetylcholine Receptors as Novel Drug Targets. ''Journal of Pharmacology and Experimental Therapeutics''. 2000; 292:461-467.</ref><ref>{{Cite pmid|16185161}}</ref><ref>{{Cite pmid|17662959}}</ref><ref>{{Cite pmid|18508600}}</ref>


== References == == References ==
{{Reflist|2}} {{Reflist|2}}



{{Stimulants}} {{Stimulants}}
{{Analgesics}} {{Analgesics}}
{{Nootropics}}
{{Cholinergics}}



{{Nicotinic acetylcholine receptor modulators}}


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