Nicotinic acetylcholine receptor ligands

Turchi J, Holley LA, Sarter M. (1995). Effects of nicotinic acetylcholine receptor ligands on behavioral vigilance in rats. Psychopharmacology (Berlin). 118(2) 195-205. 

Briggs CA, Anderson DJ, Brioni JD, Buccafusco JJ, Buckley MJ, et al. 1996. Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo. Pharmacol Biochem Behav 57 231-241. 

Breining, S.R. 2004. Recent developments in the synthesis of nicotinic acetylcholine receptor ligands. Curr Top Med Chem 4, 609-629. 

Novel 2-(2 -furo[3,2-6]pyridinylpyrrolidines potent neuronal nicotinic acetylcholine receptor ligands. Bioorg. Med. Chem. Lett. 7,... 

Lin, N.-H., Carrera, G.M., Anderson, D.J., 1994. Synthesis and evaluation of nicotine analogs as neuronal nicotinic acetylcholine receptor ligands. J. Med. Chem. 37, 3542-3553. 

D.L., Decker, M.W., Brioni, J.D., Buckley, M.J., Rodrigues, A.D., Marsh, K.G., Anderson, D.J., Buccafusco, J.J., Prendergast, M.A., Sullivan, J.P., Williams, M., Americ, S.P., Holladay, M.W., 1997. Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmeth-oxy)pyridine (ABT-089) an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties. J. Med. Chem. 40, 385-390. 

Schmitt, J.D., Sharpies, C.G.V., Caldwell, W.S., 1998. Aromatic-cation interactions in nicotinic acetylcholine receptor ligand binding. In Book of Abstracts, 216th ACS National Meeting, Boston. American Chemical Society, Washington, DC, MEDI-153. 

The open channel has in most cases a selective permeability, allowing a restricted class of ions to flow,for example Na+, K+, Ca++ or Cl- and, accordingly, these channels are called Na+-channels, K+-channels, Ca -channels and Cr-channels. In contrast, cation-permeable channels with little selectivity reject all anions but discriminate little among small cations. Little is known about the structures and functions of these non-selective cation channels [1], and so far only one of them, the nicotinic acetylcholine receptor (nAChR, see Nicotinic Receptors), has been characterized in depth [2, 3]. The nAChR is a ligand-gated channel (see below) that does not select well among cations the channel is even permeable to choline, glycine ethylester and tris buffer cations. A number of other plasma... 

Changeux, JP (1990) The nicotinic acetylcholine receptor an allosteric protein protot5q)e of ligand-gated ion channels. Trends Pharmacol. Sci. 11 485M92. 

Figure 2.1 Diagram of nicotinic acetylcholine receptor (nAChR) structure. A top view of (A) an a7 nAChR and (B) a p2 nAChR shows that homomeric and heteromeric classes of nAChRs are both pentameric in structure. Each subunit is made up of four transmembrane domains with the M2 domain making up the ion pore. (C) A side view of the four transmembrane regions shows the N terminus, C terminus, and large M3-M4 intracellular loop that make up each nAChR subunit. The extracellular loops are available for binding to ligands and the intracellular loop is available for regulation of the nAChR by intracellular signaling proteins.

Lukas, R. J. Effects of chronic nicotinic ligand exposure on functional activity of nicotinic acetylcholine receptors expressed by cells of the PC12 rat pheochromocytoma or the TE671/RD human clonal line. J. Neurochem. 56 1134, 1991. 

Gopalakrishnan, M., Molinari, E., Sullivan, J. Regulation of human 0 ,P2 neuronal nicotinic acetylcholine receptors by cholinergic channel ligands and second messenger pathways. Mol. Pharmacol. 52 524, 1997. 

Some quinolizine derivatives are employed as drugs. One of them is flumequine 280, a member of the quinolone family of antibacterial agents. Cytisine 9 is a ligand of the nicotinic acetylcholine receptor that acts primarily as a cholinomimetic at the ganglionar level, being used as a respiratory stimulant in some countries. Cytisine analogues with improved ability to cross the blood-brain barrier have also been developed <1999FA438>. 

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