Nicotinic agents

Zhang, X., Gong, Z.-H., Hellstrom-Lindahl, E., Nordberg, A. Regulation of a4(32 nicotinic acetylcholine receptors in M10 cells following treatment with nicotinic agents. Neuroreport. 6 313, 1994. 

Colom LV, Christie BR, Biand BH. (1988). Cinguiate ceii discharge patterns reiated to hippocampal EEG and their modulation by muscarinic and nicotinic agents. Brain Res. 460(2) 329-38. 

Newhouse et al. 1990 Sahakian et al. 1989]. First results indicate that nicotinic agents primarily enhance attention. In some patients, they also have been found to increase anxiety. [For further information, see Newhouse, Chapter 35, in this volume.]... 

Newhouse PA, Potter A, Lenox RH Effects of nicotinic agents on human cognition possible therapeutic applications in Alzheimer s and Parkinson s diseases. Med Chem Res 2 628-642, 1993... 

ChCMs look promising for the treatment of anxiety, but further research is warranted. Lobeline appears to be equipotent or better than nicotine in reducing anxiety without contributing to a depressive state.43 Once again, peripheral side effects with lobeline and current nicotinic agents have limited the discovery of an ChCM, to date, for use in this area. However, this is another strong area of potential for the development of centrally specific analogs. 

Although the antinociceptive potential of the natural product nicotine, an unselective nAChR agonist, was noticed as early as 1932 (Davis et al., 1932 Sahley and Berntson, 1979 Aceto et al., 1997 Rao et al., 1996 review Badio et al., 1995) interest in antinociceptive nicotinic agents was virtually non-existent for several decades. This changed dramatically in 1992 when another natural nACh receptor agonist was discovered and reported to be at least 200 times more potent than morphine (Spande et al., 1992 Holladay et al., 1997 Flores et al., 1999 Decker et al., 2001) ... 

An EHT calculation on the potent nicotinic agent phenylcholine ether showed that this molecule prefers a gauche conformation of the hetero-... 

Some aromatic ethers of choline display marked nicotinic activity, but they are inactive at muscarinic sites (94). The o-tolyl ether of choline is a potent ganglionic stimulant (95), but the 2,6-xylyl ether of choline is inert as a nicotinic agent (96). 

From a study of insecticidal nicotinic agents (114)imidacloprid (67) was reported to... 

The crystal structures of certain nicotinic agents, for example, acetyl a-methylcholine (32)and lactoylcholine (17in Table 2.1), have torsion angle (rg and T3) features similar to most muscarinic agents (262). In eontrast, some cyclic analogs of aryl choline ethers exhibit maximum nicotinic effects when the Tg is antiplanar ("transoid") (98). 

Newhouse, P.A., Kelton, M., 1999. Clinical aspects of nicotinic agents therapeutic applications in central nervous system disorders. In Clementi, F., Gotti, C., Fomasari, D. (Eds.), Handbook of Experimental Pharmacology Neuronal Nicotinic Receptors. Springer, Heidelberg, in press. 

Meyer, E.M., Tay, E.T., Zoltewicz, J.A., King, M.A., Papke, R.L., de Fiebre, C.M., 1998a. Neuroprotective and memory-related actions of novel alpha-7 nicotinic agents with different mixed agonist/antagonist properties. J. Pharmacol. Exp. Ther. 284, 1026-1032. 

In an immunochemical approach to learning more about the receptor site, an antibody was prepared against choline phenyl ether 12.86) in the rabbit. Unfortunately, when this antibody was used as a model for nicotinic receptors, it was found unable to distinguish between muscarinic and nicotinic agents, nor between agonists and antagonists (Marlow, Metcalf and Burgen, 1969). 

Perspectives of the cholinergic approach Anticholinesterases M/muscarinic agonists Nicotinic agents Glutamatergic approach Medicinal chemistry... 

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