ArticleBritish journal of pharmacology2013
CC4, a dimer of cytisine, is a selective partial agonist at α4β2/α6β2 nAChR with improved selectivity for tobacco smoking cessation.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pooled it
- Neuropharmacology of Nicotine Addiction and Therapeutic Strategies for Smoking Cessation.Biology · 2026Review
- Copper-Mediated Homocoupling ofMolecules (Basel, Switzerland) · 2025Article
- Potential uses of cytisine for smoking cessation in menopausal women - literature summary.Przeglad menopauzalny = Menopause review · 2023Article
- The Role of Physical Exercise in Opioid Substitution Therapy: Mechanisms of Sequential Effects.International journal of molecular sciences · 2023Review
- Article
- Nicotinic Acetylcholine Receptor Accessory Subunits Determine the Activity Profile of Epibatidine Derivatives.Molecular pharmacology · 2020Article
- Behavioural and pharmacological profiles of zebrafish administrated pyrrolidinyl benzodioxanes and prolinol aryl ethers with high affinity for heteromeric nicotinic acetylcholine receptors.Psychopharmacology · 2020Article
- National survey of smoking cessation provision in China.Tobacco induced diseases · 2019Article
- Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors.Current neuropharmacology · 2018Review
- Attenuated nicotine-like effects of varenicline but not other nicotinic ACh receptor agonists in monkeys receiving nicotine daily.British journal of pharmacology · 2016Article
- The twin drug approach for novel nicotinic acetylcholine receptor ligands.Bioorganic & medicinal chemistry · 2015Article
- Orthosteric and Allosteric Ligands of Nicotinic Acetylcholine Receptors for Smoking Cessation.Frontiers in molecular neuroscience · 2015Review
- The cytisine derivatives, CC4 and CC26, reduce nicotine-induced conditioned place preference in zebrafish by acting on heteromeric neuronal nicotinic acetylcholine receptors.Psychopharmacology · 2014Article
- The novel α7β2-nicotinic acetylcholine receptor subtype is expressed in mouse and human basal forebrain: biochemical and pharmacological characterization.Molecular pharmacology · 2014Article
- Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish.Psychopharmacology · 2014Article
- Differential modulation of brain nicotinic acetylcholine receptor function by cytisine, varenicline, and two novel bispidine compounds: emergent properties of a hybrid molecule.The Journal of pharmacology and experimental therapeutics · 2013Article
- Nicotine-modulated subunit stoichiometry affects stability and trafficking of α3β4 nicotinic receptor.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
background and purposeMany of the addictive and rewarding effects of nicotine are due to its actions on the neuronal nicotinic ACh receptor (nAChR) subtypes expressed in dopaminergic mesocorticolimbic cells. The partial agonists, cytisine and varenicline, are helpful smoking cessation aids. These drugs have a number of side effects that limit their usefulness. The aim of this study was to investigate the preclinical pharmacology of the cytisine dimer1,2-bisN-cytisinylethane (CC4). EXPERIMENTAL APPROACH: The effects of CC4 on nAChRs were investigated using in vitro assays and animal behaviours. KEY
resultsWhen electrophysiologically tested using heterologously expressed human subtypes, CC4 was less efficacious than cytisine on neuronal α4β2, α3β4, α7 and muscle-type receptors, and had no effect on 5-hydroxytryptamine3 receptors. Acting through α4β2 and α6β2 nAChRs, CC4 is a partial agonist of nAChR-mediated striatal dopamine release and, when co-incubated with nicotine, prevented nicotine's maximal effect on this response. In addition, it had low affinity for, and was less efficacious than nicotine and cytisine on the α3β4 and α7-nAChR subtypes. Like cytisine and nicotine, CC4-induced conditioned place preference (CPP), and its self-administration shows an inverted-U dose-response curve. Pretreatment with non-reinforcing doses of CC4 significantly reduced nicotine-induced self-administration and CPP without affecting motor functions. CONCLUSION AND IMPLICATIONS: Our in vitro and in vivo findings reveal that CC4 selectively reduces behaviours associated with nicotine addiction consistent with the partial agonist selectivity of CC4 for β2-nAChRs. The results support the possible development of CC4 or its derivatives as a promising drug for tobacco smoking cessation.
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