ArticleThe Journal of pharmacology and experimental therapeutics2015
R-(+) and S-(-) isomers of cotinine augment cholinergic responses in vitro and in vivo.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Cortical acetylcholine response to deep brain stimulation of the basal forebrain in mice.Journal of neurophysiology · 2025Article
- Cortical Acetylcholine Response to Deep Brain Stimulation of the Basal Forebrain.bioRxiv : the preprint server for biology · 2024Article
- The involvement of mesolimbic dopamine system in cotinine self-administration in rats.Behavioural brain research · 2022Article
- Early-life nicotine or cotinine exposure produces long-lasting sleep alterations and downregulation of hippocampal corticosteroid receptors in adult mice.Scientific reports · 2021Article
- Differential effects of alkaloids on memory in rodents.Scientific reports · 2021Article
- Self-Administration of Cotinine in Wistar Rats: Comparisons to Nicotine.The Journal of pharmacology and experimental therapeutics · 2021Article
- Cholinergic Receptor Modulation as a Target for Preventing Dementia in Parkinson's Disease.Frontiers in neuroscience · 2021Review
- Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.Frontiers in behavioral neuroscience · 2021Review
- Pyridine alkaloids with activity in the central nervous system.Bioorganic & medicinal chemistry · 2020Review
- Effects of nicotine, nornicotine and cotinine, alone or in combination, on locomotor activity and ultrasonic vocalization emission in adult rats.Psychopharmacology · 2020Article
- Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in AβAntioxidants (Basel, Switzerland) · 2020Article
- Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling.Frontiers in pharmacology · 2020Article
- Strategies for the Treatment of Parkinson's Disease: Beyond Dopamine.Frontiers in aging neuroscience · 2020Article
- Molecular Modulation of Human α7 Nicotinic Receptor by Amyloid-β Peptides.Frontiers in cellular neuroscience · 2019Article
- Intranasal Cotinine Plus Krill Oil Facilitates Fear Extinction, Decreases Depressive-Like Behavior, and Increases Hippocampal Calcineurin A Levels in Mice.Molecular neurobiology · 2018Article
- Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.Molecular neurobiology · 2018Review
- Effects of Nicotine on Alcohol Drinking in Female Mice Selectively Bred for High or Low Alcohol Preference.Alcoholism, clinical and experimental research · 2018Article
- Molecular Insights Into Memory-Enhancing Metabolites of Nicotine in Brain: A Systematic Review.Frontiers in neuroscience · 2018Article
- Nicotinic ligands as multifunctional agents for the treatment of neuropsychiatric disorders.Biochemical pharmacology · 2015Review
- The nicotine metabolite, cotinine, alters the assembly and trafficking of a subset of nicotinic acetylcholine receptors.The Journal of biological chemistry · 2015Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The nicotine metabolite cotinine (1-methyl-5-[3-pyridynl]-2-pyrrolidinone), like its precursor, has been found to exhibit procognitive and neuroprotective effects in some model systems; however, the mechanism of these effects is unknown. In this study, both the R-(+) and S-(-) isomers of cotinine were initially evaluated in an extensive profiling screen and found to be relatively inactive across a wide range of potential pharmacologic targets. Electrophysiological studies on human α4β2 and α7 nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes confirmed the absence of agonistic activity of cotinine at α4β2 or α7 nAChRs. However, a significant increase in the current evoked by a low concentration of acetylcholine was observed at α7 nAChRs exposed to 1.0 μM R-(+)- or S-(-)-cotinine. Based on these results, we used a spontaneous novel object recognition (NOR) procedure for rodents to test the hypothesis that R-(+)- or S-(-)-cotinine might improve recognition memory when administered alone or in combination with the Alzheimer's disease (AD) therapeutic agent donepezil. Although both isomers enhanced NOR performance when they were coadministered with donepezil, neither isomer was active alone. Moreover, the procognitive effects of the drug combinations were blocked by methyllycaconitine and dihydro-β-erythroidine, indicating that both α7 and α4β2 nAChRs contribute to the response. These results indicate that cotinine may sensitize α7 nAChRs to low levels of acetylcholine (a previously uncharacterized mechanism), and that cotinine could be used as an adjunctive agent to improve the effective dose range of cholinergic compounds (e.g., donepezil) in the treatment of AD and other memory disorders.
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