Neuronal nicotinic acetylcholine receptors - targets for the development of drugs to treat cognitive impairment associated with schizophrenia and Alzheimer's disease.
Nicotinic acetylcholine receptors (nAChR) have been strongly implicated as therapeutic targets for treating cognitive deficits in disorders such as schizophrenia and Alzheimer's disease (AD). In particular alpha7 and alpha4beta2 subtype-selective nAChR agonists and partial agonists have been developed as potential candidates for the treatment of schizophrenia, cognitive disorders (including Alzheimer's disease), and inflammation. Further development of positive allosteric modulators and antagonists were also recently reported in the literature. In this review we will cover recent developments focused on the above mentioned nAChR subtypes, starting from the most advanced clinical candidate followed by an overview of literature compounds where potency, selectivity, central nervous system access, pharmacological activity and pharmacokinetic properties are disclosed.
Haydar
Simon N
SN
Chemical Sciences, Wyeth Research, Princeton, NJ 08543, USA. haydars@wyeth.com
Dunlop
John
J
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003072:Cognition Disorders / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D055808:Drug Discovery; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic