Aug 31, 2012

The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction

The International Journal of Neuropsychopharmacology
Pradeep J NathanEdward T Bullmore

Abstract

Episodic memory deficits are a core feature of neurodegenerative disorders. Muscarinic M(1) 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 M(1) 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 M(1) receptor mediated neurotransmission in humans with GSK1034702 improves memory encoding potentially by modulating hippocampal function. Hence, selective M(1) receptor allosteric agonists may have therapeutic benefits i...Continue Reading

  • References47
  • Citations25

References

Mentioned in this Paper

Cessation of Smoking
Neurodegenerative Disorders Pathway
Synaptic Transmission
Alzheimer's Disease
Cross-Over Studies
Memory Disorders
Genus Hippocampus
Addictive Behavior
Structure of Hippocampal Formation
Entire Hippocampus

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