The DOI matches its Crossref record; 90 of the 93 references it cites were found in a registry or an index.
Neuronal nicotinic receptors: A perspective on two decades of drug discovery research
Abstract
Neuronal nicotinic acetylcholine receptors (nAChRs) have been a target for drug discovery efforts, primarily for CNS indications, for the past two decades. While nicotine and related natural products have been used for smoking cessation in various formulations (e.g., gum, spray, patches), it was only in 2006 with the launch of varenicline (Chantix) by Pfizer for smoking cessation that a new chemical entity (NCE) originating from a rational medicinal chemistry effort targeting neuronal AChRs was approved. The current overview outlines the chronology of drug discovery efforts in nAChRs from the cloning of the receptor family in the 1980s, to initial research efforts at SIBIA, R.J. Reynolds and Abbott, to the current industry-wide interest in nAChR agonists as novel therapeutics for pain, schizophrenia and Alzheimer's Disease. Key events in the evolution of the nAChR field were the development of high throughput electrophysiological screening tools that provided the means to enable lead optimization efforts in medicinal chemistry and the discovery by John Daly at the NIH of the frog alkaloid, epibatidine, that provided the framework for the discovery of ABT-594, an alpha4beta2 agonist that is 200 times more potent than morphine as an analgesic. Over the next decade, it is anticipated that additional NCEs including antagonists and allosteric modulators (both positive and negative), interacting with various nAChR subtypes, will be advanced to the clinic in areas of high unmet medical need, e.g., pain, neurodegeneration, to provide novel medications with improved efficacy.
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“Neuronal nicotinic acetylcholine receptors (nAChRs) are a key target of drug discovery efforts for nicotine dependence, as well as for neuropsychiatric conditions (3).”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [3]
Citations
Cites
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3 of the 93 references couldn’t be matched to a known paper.
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Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system
Taly, A., Corringer, P., Guédin, D., Lestage, P. J., & Changeux, J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2927 · Cited by 743
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Nicotinic acetylcholine receptors: From basic science to therapeutics
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Nicotinic ACh receptors as therapeutic targets in CNS disorders
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Metadata
- Authors
- Arneric, S. P., Holladay, M., & Williams, M.
- Affiliations
- Northwestern University (US)
- ORCID
- Williams, Michael
- Venue
- Biochemical Pharmacology
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 74
- Issue
- 8
- Pages
- 1092-1101
- ISSN
- 0006-2952 (ISSN-L)
- OpenAlex
- W2080186118
- Cited by
- 208
- References
- 93
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 12 · 2015: 14 · 2014: 9 · 2013: 19 · 2012: 16
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- neuronal nicotinic acetylcholine receptors, nicotinic agonists, history of drug discovery, varenicline, smoking cessation, epibatidine, alpha4beta2 receptor, analgesics, schizophrenia, Alzheimer's disease, pain, allosteric modulators, receptor antagonists, receptor cloning
- MeSH terms
- Animals, Cognition, Drug Industry, Humans, Neurons, Pain, Receptors, Nicotinic, Schizophrenia, Drug Design, Smoking Cessation
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