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The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction
- Source :
- International Journal of Neuropsychopharmacology. 16:721-731
- Publication Year :
- 2013
- Publisher :
- Oxford University Press (OUP), 2013.
-
Abstract
- Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M1 receptors play a critical role in modulating learning and memory and are highly expressed in the hippocampus. We examined the effect of GSK1034702, a potent M1 receptor allosteric agonist, on cognitive function, and in particular episodic memory, in healthy smokers using the nicotine abstinence model of cognitive dysfunction. The study utilized a randomized, double-blind, placebo-controlled, cross-over design in which 20 male nicotine abstained smokers were tested following single doses of placebo, 4 and 8 mg GSK1034702. Compared to the baseline (nicotine on-state), nicotine abstinence showed statistical significance in reducing immediate (p=0.019) and delayed (p=0.02) recall. GSK1034702 (8 mg) significantly attenuated (i.e. improved) immediate recall (p=0.014) but not delayed recall. None of the other cognitive domains was modulated by either nicotine abstinence or GSK1034702. These findings suggest that stimulating M1 receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective M1 receptor allosteric agonists may have therapeutic benefits in disorders of impaired learning including Alzheimer's disease.
- Subjects :
- Adult
Male
Agonist
Nicotine
medicine.drug_class
Memory, Episodic
media_common.quotation_subject
Hippocampus
Pharmacology
Young Adult
Allosteric Regulation
Double-Blind Method
Muscarinic acetylcholine receptor
medicine
Humans
Pharmacology (medical)
Episodic memory
media_common
Cross-Over Studies
Recall
Receptor, Muscarinic M1
Smoking
Muscarinic acetylcholine receptor M1
Middle Aged
Abstinence
Behavior, Addictive
Psychiatry and Mental health
Benzimidazoles
Smoking Cessation
Cognition Disorders
Psychology
Neuroscience
medicine.drug
Subjects
Details
- ISSN :
- 14695111 and 14611457
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- International Journal of Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....d2830570e425f54ac95c9af1dd4605e2