Targeting neuronal nicotinic receptors: a path to new therapies.
The structural heterogeneity, the ubiquity of anatomical distribution, and the demonstrated modulation of biological functions is consistent with the view that nicotinic cholinergic signaling plays a key regulatory role in the brain and influences a number of neuronal processes including sensory processing, motor activity, and cognitive function. It has become evident that perturbation of nicotinic cholinergic neurotransmission can result in diverse CNS pathologies providing the potential for therapeutic intervention in a number of neurodegenerative, neuropsychiatric and neurological disorders. This review will provide a status on the rationale for neuronal therapies targeting neuronal nicotinic receptors (nAChRs) and discusses the multifaceted beneficial effects than can be achieved through manipulation of cholinergic pharmacology. Recent advances and issues relating to rational drug design based on the structure of acetylcholine binding protein are discussed.
Bencherif
Merouane
M
Targacept Inc., 200 East First Street, Suite 300, Winston-Salem, NC 27101-4165, USA. merouane.bencherif@targacept.com
Schmitt
Jeffrey D
JD
D000818:Animals; D015195:Drug Design; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy; D009422:Nervous System Diseases / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D011978:Receptors, Nicotinic / Q000187:drug effects*
D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic