Quaternary ammonium 3-(aminoethoxy)pyridines as antinociceptive agents

3-(4-Aminobutyn-1-yl)pyridines: binding at α4β2 nicotinic cholinergic receptors

“…Quaternization (via methylation) of nicotine has little effect on affinity 18 whereas quaternization of the N,N-dimethyl analogue of 2 increased affinity by about 40-fold. 19 In the present study, N-methylation of 6b had essentially no effect on affinity. Although additional compounds might need to be studied, a general conclusion that can be tentatively reached is that alteration of the terminal amine group of 6-series compounds, more so than alterations in the pyridyl portion, results in greater disparity of results when compared with the pyridyl ether (i.e., 2-) series (or the aminomethylpyridine series) of compounds.…”

Novel 1-(1-benzyl-1H-indol-3-yl)-N,N,N-trimethylmethanaminium iodides are competitive antagonists for the human α4β2 and α7 nicotinic acetylcholine receptors

“…trimethylammonium group increases ligand affinity to nAChRs. [9][10][11][12][13][14] In this paper, we describe the synthesis of a series of novel 1-(1-benzyl-1H-indol-3-yl)-N,N,N-trimethylmethanaminium iodide derivatives by using a one-pot microwave heating procedure. Subsequently, the pharmacological activity of these compounds at human (h) a7 and a4b2 nAChRs was determined by Ca 2+ inux assays.…”

α4β2 nACh Receptor pharmacophore models

“…6,9,17 Furthermore, quaternization of nicotine results only in slightly enhanced affinity 9 whereas, in contrast, quaternization of AXP-type compounds enhances their affinity by > 50-fold. 19 It might not be expected that the quaternary amine analogue of nicotine would readily form a hydrogen bond with water whereas with the longer AXP analogues, water would not be necessary. Hence, the different results might be rationalized in this manner.…”