Tebanicline (Ebanicline, ABT-594) is a potent synthetic nicotinic (non-opioid) analgesic drug developed by Abbott. It was developed as a less toxic analogue of the potent poison dart frog-derived compound epibatidine, which is some 200x stronger than morphine as an analgesic but produces extremely dangerous toxic side effects.[1][2] Like epibatidine, tebanicline showed potent analgesic activity against neuropathic pain in both animal and human trials, but with far less toxicity than its parent compound.[3][4][5][6][7][8]
Tebanicline got as far as Phase II trials in humans,[9] but was dropped from further development due to unacceptable incidence of gastrointestinal side effects.[10] However further research in this area is ongoing,[11][12][13][14] 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.[15][16][17][18]
^Bannon, A. W.; Decker, M. W.; Holladay, M. W.; Curzon, P.; Donnelly-Roberts, D.; Puttfarcken, P. S.; Bitner, R. S.; Diaz, A.; Dickenson, A. H.; Porsolt, R. D.; Williams, M.; Arneric, S. P. (1998). "Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors". Science279 (5347): 77–81. Bibcode:1998Sci...279...77B. doi:10.1126/science.279.5347.77. PMID9417028.
^Holladay, M.; Wasicak, J.; Lin, N.; He, Y.; Ryther, K.; Bannon, A.; Buckley, M.; Kim, D.; Decker, M.; Anderson, D. J.; Campbell, J. E.; Kuntzweiler, T. A.; Donnelly-Roberts, D. L.; Piattoni-Kaplan, M.; Briggs, C. A.; Williams, M.; Arneric, S. P. (1998). "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 of Medicinal Chemistry41 (4): 407–412. doi:10.1021/jm9706224. PMID9484491.
^Donnelly-Roberts, D. L.; Puttfarcken, P. S.; Kuntzweiler, T. A.; Briggs, C. A.; Anderson, D. J.; Campbell, J. E.; Piattoni-Kaplan, M.; McKenna, D. G.; Wasicak, J. T.; Holladay, M. W.; Williams, M.; Arneric, S. P. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization". The Journal of Pharmacology and Experimental Therapeutics285 (2): 777–786. PMID9580626.
^Bannon, A. W.; Decker, M. W.; Curzon, P.; Buckley, M. J.; Kim, D. J.; Radek, R. J.; Lynch, J. K.; Wasicak, J. T.; Lin, N. H.; Arnold, W. H.; Holladay, M. W.; Williams, M.; Arneric, S. P. (1998). "ABT-594 (R)-5-(2-azetidinylmethoxy)-2-chloropyridine: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. In vivo characterization". The Journal of Pharmacology and Experimental Therapeutics285 (2): 787–794. PMID9580627.
^Decker, M. W.; Bannon, A. W.; Buckley, M. J.; Kim, D. J.; Holladay, M. W.; Ryther, K. B.; Lin, N. H.; Wasicak, J. T.; Williams, M.; Arneric, S. P. (1998). "Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice". European Journal of Pharmacology346 (1): 23–33. doi:10.1016/S0014-2999(98)00042-9. PMID9617748.
^Kesingland, A. C.; Gentry, C. T.; Panesar, M. S.; Bowes, M. A.; Vernier, J. M.; Cube, R.; Walker, K.; Urban, L. (2000). "Analgesic profile of the nicotinic acetylcholine receptor agonists, (+)-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain". Pain86 (1–2): 113–118. doi:10.1016/S0304-3959(00)00233-5. PMID10779668.
^Lynch Jj, 3.; Wade, C.; Mikusa, J.; Decker, M.; Honore, P. (2005). "ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model". European Journal of Pharmacology509 (1): 43–48. doi:10.1016/j.ejphar.2004.12.034. PMID15713428.
^Decker, M.; Meyer, M.; Sullivan, J. (2001). "The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control". Expert Opinion on Investigational Drugs10 (10): 1819–1830. doi:10.1517/13543784.10.10.1819. PMID11772288.
^Meyer, MD (2006). "Neuronal Nicotinic Acetylcholine Receptors as a Target for the Treatment of Neuropathic Pain". Drug Development Research67 (4): 355–359. doi:10.1002/ddr.20099.
^Zhang, C.; Ge, Z.; Cheng, T.; Li, R. (2006). "Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594". Bioorganic & Medicinal Chemistry Letters16 (7): 2013–2016. doi:10.1016/j.bmcl.2005.12.073. PMID16412637.
^Bunnelle, W.; Daanen, J.; Ryther, K.; Schrimpf, M.; Dart, M.; Gelain, A.; Meyer, M.; Frost, J.; Anderson, D.; Buckley, M.; Curzon, P.; Cao, Y. J.; Puttfarcken, P.; Searle, X.; Ji, J.; Putman, C. B.; Surowy, C.; Toma, L.; Barlocco, D. (2007). "Structure-activity studies and analgesic efficacy of N-(3-pyridinyl)-bridged bicyclic diamines, exceptionally potent agonists at nicotinic acetylcholine receptors". Journal of Medicinal Chemistry50 (15): 3627–3644. doi:10.1021/jm070018l. PMID17585748.
^Joshi, S.; Mikusa, J.; Weaver, B.; Honore, P. (2008). "Morphine and ABT-594 (a nicotinic acetylcholine agonist) exert centrally mediated antinociception in the rat cyclophosphamide cystitis model of visceral pain". The journal of pain : official journal of the American Pain Society9 (2): 146–156. doi:10.1016/j.jpain.2007.09.004. PMID18088559.
^Lloyd, GK; Williams, M (2000). "Neuronal Nicotinic Acetylcholine Receptors as Novel Drug Targets". Journal of Pharmacology and Experimental Therapeutics292: 461–467.
^Vincler, M. (2005). "Neuronal nicotinic receptors as targets for novel analgesics". Expert Opinion on Investigational Drugs14 (10): 1191–1198. doi:10.1517/13543784.14.10.1191. PMID16185161.
^Arneric, S.; Holladay, M.; Williams, M. (2007). "Neuronal nicotinic receptors: a perspective on two decades of drug discovery research". Biochemical Pharmacology74 (8): 1092–1101. doi:10.1016/j.bcp.2007.06.033. PMID17662959.
^Jain, K. K. (2004). "Modulators of nicotinic acetylcholine receptors as analgesics". Current opinion in investigational drugs (London, England : 2000)5 (1): 76–81. PMID14983978.