Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Neurochem Int
2019 Dec 01;131:104552. doi: 10.1016/j.neuint.2019.104552.
Show Gene links
Show Anatomy links
Selectivity of (±)-citalopram at nicotinic acetylcholine receptors and different inhibitory mechanisms between habenular α3β4* and α9α10 subtypes.
Arias HR
,
Jin XT
,
Gallino S
,
Peng C
,
Feuerbach D
,
García-Colunga J
,
Elgoyhen AB
,
Drenan RM
,
Ortells MO
.
???displayArticle.abstract???
The inhibitory activity of (±)-citalopram on human (h) α3β4, α4β2, and α7 nicotinic acetylcholine receptors (AChRs) was determined by Ca2+ influx assays, whereas its effect on rat α9α10 and mouse habenular α3β4* AChRs by electrophysiological recordings. The Ca2+ influx results clearly establish that (±)-citalopram inhibits (IC50's in μM) hα3β4 AChRs (5.1 ± 1.3) with higher potency than that for hα7 (18.8 ± 1.1) and hα4β2 (19.1 ± 4.2) AChRs. This is in agreement with the [3H]imipramine competition binding results indicating that (±)-citalopram binds to imipramine sites at desensitized hα3β4 with >2-fold higher affinity than that for hα4β2. The electrophysiological, molecular docking, and in silico mutation results indicate that (±)-citalopram competitively inhibits rα9α10 AChRs (7.5 ± 0.9) in a voltage-independent manner by interacting mainly with orthosteric sites, whereas it inhibits a homogeneous population of α3β4* AChRs at MHb (VI) neurons (7.6 ± 1.0) in a voltage-dependent manner by interacting mainly with a luminal site located in the middle of the ion channel, overlapping the imipramine site, which suggests an ion channel blocking mechanism. In conclusion, (±)-citalopram inhibits α3β4 and α9α10 AChRs with higher potency compared to other AChRs but by different mechanisms. (±)-Citalopram also inhibits habenular α3β4*AChRs, supporting the notion that these receptors are important endogenous targets related to their anti-addictive activities.
???displayArticle.pubmedLink???
31545995
???displayArticle.pmcLink???PMC7221482 ???displayArticle.link???Neurochem Int ???displayArticle.grants???[+]
Andreasen,
Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: a comparison of SSR180711 and PNU-282987.
2012, Pubmed
Andreasen,
Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: a comparison of SSR180711 and PNU-282987.
2012,
Pubmed
Andreasen,
Subtype-selective nicotinic acetylcholine receptor agonists enhance the responsiveness to citalopram and reboxetine in the mouse forced swim test.
2011,
Pubmed
,
Xenbase
Andreasen,
Nicotine reverses anhedonic-like response and cognitive impairment in the rat chronic mild stress model of depression: comparison with sertraline.
2011,
Pubmed
Angelone,
Effects of fluvoxamine and citalopram in maintaining abstinence in a sample of Italian detoxified alcoholics.
1998,
Pubmed
Arias,
Selectivity of coronaridine congeners at nicotinic acetylcholine receptors and inhibitory activity on mouse medial habenula.
2017,
Pubmed
Arias,
Bupropion and its photoreactive analog (±)-SADU-3-72 interact with luminal and non-luminal sites at human α4β2 nicotinic acetylcholine receptors.
2016,
Pubmed
Arias,
Interaction of selective serotonin reuptake inhibitors with neuronal nicotinic acetylcholine receptors.
2010,
Pubmed
Arias,
Tricyclic antidepressants and mecamylamine bind to different sites in the human alpha4beta2 nicotinic receptor ion channel.
2010,
Pubmed
Arias,
Tricyclic antidepressants inhibit hippocampal α7* and α9α10 nicotinic acetylcholine receptors by different mechanisms.
2018,
Pubmed
Arias,
Different interaction between tricyclic antidepressants and mecamylamine with the human alpha3beta4 nicotinic acetylcholine receptor ion channel.
2010,
Pubmed
Ballestero,
Effects of quinine, quinidine, and chloroquine on alpha9alpha10 nicotinic cholinergic receptors.
2005,
Pubmed
,
Xenbase
Boffi,
Differential Contribution of Subunit Interfaces to α9α10 Nicotinic Acetylcholine Receptor Function.
2017,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Cheng,
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
1973,
Pubmed
Chi,
Mecamylamine attenuates the subjective stimulant-like effects of alcohol in social drinkers.
2003,
Pubmed
Christmas,
A biological pathway linking inflammation and depression: activation of indoleamine 2,3-dioxygenase.
2011,
Pubmed
Elgoyhen,
The efferent medial olivocochlear-hair cell synapse.
2012,
Pubmed
Elgoyhen,
Alpha 9: an acetylcholine receptor with novel pharmacological properties expressed in rat cochlear hair cells.
1994,
Pubmed
,
Xenbase
Elgoyhen,
alpha10: a determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells.
2001,
Pubmed
,
Xenbase
Fryer,
Antidepressants noncompetitively inhibit nicotinic acetylcholine receptor function.
1999,
Pubmed
García-Colunga,
Blockage of muscle and neuronal nicotinic acetylcholine receptors by fluoxetine (Prozac).
1997,
Pubmed
,
Xenbase
Glick,
Modulation of nicotine self-administration in rats by combination therapy with agents blocking alpha 3 beta 4 nicotinic receptors.
2002,
Pubmed
Goutman,
Cochlear hair cells: The sound-sensing machines.
2015,
Pubmed
Maisonneuve,
Anti-addictive actions of an iboga alkaloid congener: a novel mechanism for a novel treatment.
2003,
Pubmed
McCallum,
α3β4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in vivo.
2012,
Pubmed
McIntosh,
Alpha9 nicotinic acetylcholine receptors and the treatment of pain.
2009,
Pubmed
,
Xenbase
Mineur,
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis.
2010,
Pubmed
Morales-Perez,
X-ray structure of the human α4β2 nicotinic receptor.
2016,
Pubmed
Morley,
Commentary: Nicotinic Acetylcholine Receptor α9 and α10 Subunits Are Expressed in the Brain of Mice.
2018,
Pubmed
Pedretti,
VEGA--an open platform to develop chemo-bio-informatics applications, using plug-in architecture and script programming.
2004,
Pubmed
Peng,
Characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) and alpha (alpha) 10 (CHRNA10) in lymphocytes.
2004,
Pubmed
Phillips,
Scalable molecular dynamics with NAMD.
2005,
Pubmed
Plazas,
Stoichiometry of the alpha9alpha10 nicotinic cholinergic receptor.
2005,
Pubmed
,
Xenbase
Popik,
Nicotine and nicotinic receptor antagonists potentiate the antidepressant-like effects of imipramine and citalopram.
2003,
Pubmed
Quick,
Alpha3beta4 subunit-containing nicotinic receptors dominate function in rat medial habenula neurons.
1999,
Pubmed
,
Xenbase
Rezvani,
Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats.
2016,
Pubmed
Romero,
Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain.
2017,
Pubmed
Rothlin,
Direct interaction of serotonin type 3 receptor ligands with recombinant and native alpha 9 alpha 10-containing nicotinic cholinergic receptors.
2003,
Pubmed
,
Xenbase
Rothlin,
The alpha9 nicotinic acetylcholine receptor shares pharmacological properties with type A gamma-aminobutyric acid, glycine, and type 3 serotonin receptors.
1999,
Pubmed
,
Xenbase
Rothlin,
Block of the alpha9 nicotinic receptor by ototoxic aminoglycosides.
2000,
Pubmed
,
Xenbase
Sacre,
Fluoxetine and citalopram exhibit potent antiinflammatory activity in human and murine models of rheumatoid arthritis and inhibit toll-like receptors.
2010,
Pubmed
Sali,
Evaluation of comparative protein modeling by MODELLER.
1995,
Pubmed
Shih,
Differential expression and function of nicotinic acetylcholine receptors in subdivisions of medial habenula.
2014,
Pubmed
Stein,
Predictors of response to pharmacotherapy with citalopram in obsessive-compulsive disorder.
2001,
Pubmed
Trott,
AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.
2010,
Pubmed
Varia,
Treatment of generalized anxiety disorder with citalopram.
2002,
Pubmed
Verbitsky,
Mixed nicotinic-muscarinic properties of the alpha9 nicotinic cholinergic receptor.
2000,
Pubmed
,
Xenbase
