Affinity ligands and related agents for brain muscarinic and nicotinic cholinergic receptors

Abood, Leo G.; Saraswati, Manda; Lerner-Marmarosh, Nicoll; Hashmi, M.

doi:10.1016/0006-2952(93)90028-u

Cited by 6 publications

(1 citation statement)

References 12 publications

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“…Indeed, when the nonselective cholinergic agonist, carbachol, was administered, an inverse dose–response was observed. With a higher binding affinity to muscarinic acetylcholine receptors (Abood et al, 1993), lower doses of carbachol would provide more selective muscarinic activation, while higher doses would result in a relative increase in nicotinic receptor activation. Thus, in light of the negative effects nicotinic receptor activation was shown to have on cell proliferation, their increased activation by higher doses of carbachol would counteract muscarinic receptor-mediated elevations.…”

Section: Discussionmentioning

confidence: 99%

Agonist-induced restoration of hippocampal neurogenesis and cognitive improvement in a model of cholinergic denervation

Kampen

Eckman

2010

Neuropharmacology

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Loss of basal forebrain cholinergic innervation of the hippocampus and severe neuronal loss within the hippocampal CA1 region are early hallmarks of Alzheimer’s disease, and are strongly correlated with cognitive status. Various therapeutic approaches involve attempts to enhance neurotransmission or to provide some level of neuroprotection for remaining cells. An alternative approach may involve the generation of new cells to replace those lost in AD. Indeed, a simple shift in the balance between cell generation and cell loss may slow disease progression and possibly even reverse existing cognitive deficits. One potential neurogenic regulator might be acetylcholine, itself, which has been shown to play a critical role in hippocampal development. Here, we report the effects of various cholinergic compounds on indices of hippocampal neurogenesis, demonstrating a significant induction following pharmacological activation of muscarinic M1 receptors, located on hippocampal progenitors in the adult brain. This is the first report that a small-molecule agonist may induce neurogenesis in the hippocampal CA1 region. Furthermore, such treatment reversed deficits in markers of neurogenesis and spatial working memory triggered by cholinergic denervation in a rodent model. This study suggests the use of small molecule, receptor agonists may represent a novel means to trigger the restoration of specific neuronal populations lost to a variety of neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, Huntington’s and Amyotrophic Lateral Sclerosis.

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Section: Discussionmentioning

confidence: 99%