Nicotinic acetylcholine receptor agonist

Anatoxin-a is the most potent and most stereospecific nicotinic acetylcholine receptor agonist thus far identified. It is also highly selective for nicotinic receptors over muscarinic receptors. The molecular parameters which influence the binding affinity, channel activation, channel blockade, and receptor desensitization are being studied. Modifications of the carbonyl and amine moieties can reduce or nearly eliminate the receptor agonist potency of the compounds and also determine the channel blocking characteristics. 

Decker, M. W., Meyer, M. D., Sullivan, J. P. The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control, Exp. Opin. Invest. Drugs 2001, 10, 1819-1830. 

Analgesic profile of the nicotinic acetylcholine receptors agonists, (+)-epibatidine and ABT-594 in models of persistent inflammatory and neuropathic pain. Pain 2000, 86, 113-118. 

Sullivan, J. P., Bannon, A. W. Epibatidine Pharmacological properties of a novel nicotinic acetylcholine receptor agonist and analgesic agent, CNS Drug Rev. 1996, 2, 21-39. 

In a development involving racemic products, nonactivated /V-benzyl (3-lactam 117, is shown to be opened selectively with methyllithium to yield, after intramolecular oxirane opening, the methyl ketone 118, Scheme 39. This compound is transformed through several steps into the nicotinic acetylcholine receptor agonist anatoxin-a [106]. 

Kesingland AC, Gentry CT, Panesar MS, Bowes MA, 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. Pain 86 113... 

Schneider JS, Pope-Coleman A, Van Velson M, Menzaghi F, Lloyd GK (1998) Effects of SIB-1508Y, a novel neuronal nicotinic acetylcholine receptor agonist, on motor behavior in parkinsonian monkeys. Mov Disord 73 637-642. 

Table 3.1 Nicotinic acetylcholine receptor agonists and antagonists...

Page 80, figure 9.5 Biochemistry, 42 271 -283 (2003), Chiara D.C. et al. Identification of amino acids in the nicotinic acetylcholine receptor agonist binding site and ion channel photolabeled by 4-[(3-trifluo-romethyl)-3H-diazirin-3-yl]benzoylcholine, a novel pho-toaffinity antagonist. Reproduced with permission from publisher and authors. 

Sutherlan4 A., Gallagher, T, Sharpies, C.G.Y, and Wonnacott, S. 2003. Synthesis of two fluoro analogues of the nicotinic acetylcholine receptor agonist UB-165. J Org Chem 68, 2475—2478. 

Decker MW, Meyer MD, Sullivan JP. The therapeutic potential 58. of nicotinic acetylcholine receptor agonists for pain control. 

Decker MW, Meyer MD. Therapeutic potential of neuronal nicotinic acetylcholine receptor agonists as novel analgesics. 59. Biochem. Pharmacol. 1999 58 917-923. 

Boess FG, de Vry J, Erb C, Flessner T, Hendrix M, Luithle J et al (2013) Pharmacological and behavioral profile of N-[(3R)-l-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141), a novel a7 nicotinic acetylcholine receptor agonist/ serotonin 5-HT3 receptor antagonist. Psychopharmacology (Berl) 227 1-17... 

In 2002, Wonnacott published the synthesis and biological evaluation of a pyridazine analog (62) of nicotinic acetylcholine receptor agonist UB-165 [45]. This aza-UB-165 analog (62) was synthesized via Negishi cross-coupling reaction on triflate 60 with pyridazin-3-ylzinc halide (59). Compound 59 could be obtained from 3-bromopyridazine (58) via lithiation and subsequent transmetalation with zinc chloride. 

Holladay, M. W., Lebold, S. A., Lin, N. H. Structure-activity relationships of nicotinic acetylcholine receptor agonists as potential treatments for dementia. Drug. Dev. Res. 1995(35), 191-213. 

Lloyd, G.K.. Menzaghi, F Bontempi, B., Suto. C.. Siegel, R., Akong, M. et al., 1998. The potential of subtype-selective neuronal nicotinic acetylcholine receptor agonists as therapeutic agents. Life Sci. 62, 1601-1606. 

Schneider, J.S., Van Velson, M., Menzaghi, F., Lloyd, G.K., 1998. Effects of the nicotinic acetylcholine receptor agonist SIB-1508Y on object retrieval performance in MPTP-treated monkeys comparison with levodopa treatment. Ann. Neurol. 43, 311-317. 

T., Donnelly-Roberts, D.L., Anderson, D.J., Campbell, J.E., Sullivan, J.P., Arneric, S.P., Holladay, M.W., 1998. Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-((S)-pyrro-lidinyDmethoxylpyridine, A-84543, a potent nicotinic acetylcholine receptor agonist. Bioorg. Med. Chem. Lett. 8, 249-254. 

Nicotinic acetylcholine receptor agonists (allosteric) (not group 4)... 

Nicotinic Acetylcholine Receptor Agonists, Target and Selectivity Aspects... 

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