Potential applications of nicotinic ligands in the laboratory and clinic

• Published in: Bioorganic & medicinal chemistry letters 2004-04, Vol.14 (8), p.1837-1839
• Main Authors: Dani, J.A, De Biasi, M, Liang, Y, Peterson, J, Zhang, L, Zhang, T, Zhou, F.M
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Animals; Biological and medical sciences; Cholinergic system; Humans; Ligands; Medical sciences; Mice; Mice, Knockout; Neurons - drug effects; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nicotinic Agonists - pharmacology; Pharmacology. Drug treatments; Protein Subunits - pharmacology; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Substrate Specificity; Synaptic Transmission - physiology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.07.036

The nicotinic acetylcholine receptor (nAChR) is a receptor, ion channel complex composed of five polypeptide subunits. There are many different nAChR subtypes constructed from a variety of different subunit combinations. This structural diversity contributes to the varied roles of nAChRs in the peripheral and central nervous system, and this diversity offers an excellent opportunity for chemists who are producing ligands. Subunit specific ligands could have wide and varied effects in the laboratory as experimental tools and in the clinic as therapeutic agents. Because presynaptic nAChRs have been shown to enhance the release of many neurotransmitters, new nicotinic ligands that potentiate nAChR activity would be very useful. Such ligands could enhance the release of various neurotransmitters during degenerative diseases that cause neurotransmitter systems to decrease their output. For example, boosting the release from cholinergic neurons would help patients with Alzheimer's disease, and boosting the release from dopaminergic neurons would help patients with Parkinson's disease. There are many different nicotinic acetylcholine receptor subtypes constructed from a variety of different subunit combinations. This extensive diversity offers an excellent opportunity for chemists who are producing nicotinic ligands. Subunit specific ligands could have wide and varied effects in the laboratory as experimental tools and in the clinic as therapeutic agents.