Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease
Abstract
To explore further the potential for cognitive enhancement utilizing nicotinic stimulation in Alzheimer's disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition. No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson's disease are warranted.
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Agonists selective for α4β2* nAChRs produce more robust and clinically promising enhancement of attention and related cognitive abilities than nicotine.
“Recent studies have indicated that agonists selective for α4β2* nAChRs produce perhaps more robust and clinically more promising enhancement of attention and related cognitive abilities (Potter et al, 1999; Wilens et al, 1999; Wilens et al, 2006; Dunbar et al, 2007; Wilens and Decker, 2007).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Potter et al, 1999
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- Authors
- Potter, A., Corwin, J., Lang, J., Piasecki, M., Lenox, R., & Newhouse, P. A.
- Affiliations
- University of Vermont (US)
- New York University (US)
- University of Pennsylvania (US)
- Venue
- Psychopharmacology
- Published
- 1999-03-17
- Volume
- 142
- Issue
- 4
- Pages
- 334-342
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2038095204
- Cited by
- 163
- References
- 31
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2019: 2 · 2018: 8 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 11 · 2012: 10
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- U.S. Public Health Service (R29-46625, M01-00109)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- ABT-418, nicotinic agonists, Alzheimer's disease, nicotinic acetylcholine receptors, cognitive enhancement, verbal learning, spatial learning and memory, memory retrieval, dementia, acute drug effects
- MeSH terms
- Aged, Alzheimer Disease, Cognition, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Hydrocortisone, Isoxazoles, Learning, Male, Memory, Middle Aged, Prolactin, Psychomotor Performance, Pyrrolidines, Nicotinic Agonists
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