Nicotinic receptors containing the alpha7 subunit: a model for rational drug design.
The neuronal nicotinic receptor has gained considerable recognition as a target, not just for combating drug addiction but also for treating a number of illnesses ranging from neurodegenerative diseases to psychotic disorders like schizophrenia. This recognition has led to a burgeoning field examining the receptor at all levels. A class of nicotinic receptors that contains the alpha7 gene product, apparently as a homomer, illustrates this multidisciplinary approach. Here, we review recent progress in our understanding of this class of receptors based on data from molecular, structural, physiological and patho-physiological studies. These studies have set the stage for rational drug design to combat disorders of the central nervous system. The studies also exemplify the cautious approach needed in developing CNS therapies and the importance of physiology in tempering drug design.
Sharma
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G
Department of Physiology and Biophysics and Neuroscience Program, University of Colorado, Denver, School of Medicine, Aurora Colorado, USA.
Vijayaraghavan
S
S
D000495:Allosteric Site; D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008956:Models, Chemical; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology*; D015398:Signal Transduction; D012907:Smoking; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D008024:Ligands; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003577:Cytochrome P-450 Enzyme System