BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders
Open accessAbstract
INTRODUCTION: Anxiety disorders are common, disabling psychiatric conditions associated with excessive worry, irritability, and physiological symptoms of stress. Following insufficient response to psychological therapies, first-line pharmacological treatments for anxiety disorders suffer from inconsistent efficacy, addiction, and intolerable side-effect profiles (e.g. sedation), especially when used inappropriately or contrary to evidence-based guidelines. Developing anxiolytics acting via cholinergic modulation may provide novel options for the treatment of anxiety disorders, without the drawbacks of existing anxiolytics. AREAS COVERED: We review pharmacological treatment of anxiety disorders and proposed mechanisms of action in relation to the associated neural circuitry. We then consider the mechanism of action, pharmacodynamics, and pharmacokinetics of the negative-allosteric modulator of the alpha7 nicotinic receptor BNC210, an investigational anxiolytic so far employed in studies of those with social anxiety disorder, post-traumatic stress disorder, and agitation in hospitalized elderly. Lastly, we consider the environment of competitor compounds for this indication, and BNC210's place within it, in both the present and near-future. EXPERT OPINION: : There is a relative paucity of data regarding BNC210, albeit the small amount of mostly non-peer reviewed data indicate it is a well-tolerated, effective anxiolytic. Phase III trials are required for proper appraisal of its utility.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Selective serotonin reuptake inhibitors cannot be used for on-demand treatment due to their slow onset of action.
“but cannot be used for on-demand treatment due to their slow onset of action.”
Selective serotonin reuptake inhibitors have been approved for the treatment of anxiety disorders, including SAD.
“Selective serotonin reuptake inhibitors have been approved for the treatment of anxiety disorders, including SAD, 7,8”
Cites
Diagnostic and Statistical Manual of Mental Disorders
American Psychiatric Association (2013) · doi:10.1176/appi.books.9780890425596 · Cited by 116,369 · see citing works
(1970) · Cited by 24,983 · see citing works
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.6.593 · Cited by 20,391 · see citing works
Kessler, R. C. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950010008002 · Cited by 12,370 · cited 1× · see citing works
“GAD is more commonly diagnosed in women at a ratio of 3:2 [16], with a mean age at onset of 21 [17].”
BackgroundEpidemiology of anxiety disorders in the 21st century
Bandelow, B., & Michaelis, S. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.3/bbandelow · Cited by 2,079 · cited 1× · see citing works
“Generalized Anxiety Disorder is a common [10], chronic”
BackgroundNicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System
Dani, J. A., & Bertrand, D. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105214 · Cited by 1,197 · cited 1× · see citing works
“Nicotinic acetylcholine receptors (nAChRs) are ionotropic ligand-gated receptor polypeptides that are activated by acetylcholine and nicotine [36,37].”
BackgroundPrakash, R. (2003) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v64n0318d · Cited by 1,031 · see citing works
Neuronal nicotinic receptors: from structure to pathology
Gotti, C., & Clementi, F. (2004) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2004.09.006 · Cited by 970 · cited 1× · see citing works
“of five α7 subunits that are primarily homomeric [38].”
BackgroundEtkin, A., Prater, K. E., Hoeft, F., Menon, V., & Schatzberg, A. F. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2009.09070931 · Cited by 550 · cited 1× · see citing works
“Imaging studies have demonstrated amygdala hyperactivity in response to threatening stimuli across anxiety disorders [23,24] which appears to be regulated through functional connections with the anterior cingulate cortex (ACC) [25,26].”
BackgroundThe Age of Onset of Anxiety Disorders: A Meta-analysis
Lijster, J. M. D., Dierckx, B., Utens, E. M. W. J., Verhulst, F. C., Zieldorff, C., Dieleman, G. C., & Legerstee, J. S. (2017) · The Canadian Journal of Psychiatry · doi:10.1177/0706743716640757 · Cited by 426 · cited 1× · see citing works
“GAD is more commonly diagnosed in women at a ratio of 3:2 [16], with a mean age at onset of 21 [17].”
BackgroundMcTeague, L. M., Rosenberg, B. M., Lopez, J. W., Carreon, D. M., Huemer, J., Jiang, Y., Chick, C. F., Eickhoff, S. B., & Etkin, A. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.18111271 · Cited by 388 · cited 1× · see citing works
“altered serotonergic projections from the raphe nuclei [7] and prefrontonal-limbic pathways [8] (see”
BackgroundNitschke, J. B., Sarinopoulos, I., Oathes, D. J., Johnstone, T., Whalen, P. J., Davidson, R. J., & Kalin, N. H. (2009) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07101682 · Cited by 375 · cited 1× · see citing works
“Imaging studies have demonstrated amygdala hyperactivity in response to threatening stimuli across anxiety disorders [23,24] which appears to be regulated through functional connections with the anterior cingulate cortex (ACC) [25,26].”
BackgroundCarter, R., Wittchen, H., Pfister, H., & Kessler, R. (2001) · Depression and Anxiety · doi:10.1002/da.1020 · Cited by 345 · cited 3× · see citing works
“anxiety disorders and other classes of affective disorders, for example, 59% of those with GAD have a lifetime comorbidity with MDD [6].”
BackgroundInfluentialBenzodiazepines: Uses, Dangers, and Clinical Considerations
Edinoff, A. N., Nix, C. A., Hollier, J., Sagrera, C. E., Delacroix, B. M., Abubakar, T., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (2021) · Neurology International · doi:10.3390/neurolint13040059 · Cited by 340 · cited 1× · see citing works
“Benzodiazepines are often offered as second-line treatments for anxiety as they are fast-acting compounds available relatively cheaply, albeit they often carry more debilitating side effects such as addiction and sedation [28].”
BackgroundStructure and gating mechanism of the α7 nicotinic acetylcholine receptor
Noviello, C., Gharpure, A., Mukhtasimova, N., Cabuco, R., Baxter, L., Borek, D., Sine, S. M., & Hibbs, R. E. (2021) · Cell · doi:10.1016/j.cell.2021.02.049 · Cited by 303 · cited 1× · see citing works
“NAChRs more broadly are nonselective cation channels, with the α7 subtype particularly permeable to calcium [39], in addition to sodium [40].”
BackgroundStrawn, J. R., Geracioti, L., Rajdev, N., Clemenza, K., & Levine, A. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1491966 · Cited by 214 · see citing works
Robinson, O. J., Charney, D. R., Overstreet, C. M., Vytal, K. E., & Grillon, C. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2011.11.096 · Cited by 196 · cited 2× · see citing works
“A recent study demonstrated that pharmacological reductions in amygdalarACC functional connectivity were associated with significantly reduced amygdala reactivity to fearful faces in GAD patients [21], lending credence to the hypothesis that the prefrontal-limbic system is a relevant substrate in relation to GAD.”
BackgroundGenetics of generalized anxiety disorder and related traits
Gottschalk, M. G., & Domschke, K. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.2/kdomschke · Cited by 194 · cited 1× · see citing works
“The contribution of hereditary factors is approximately 30% [14], with the remaining 70%”
BackgroundAn effect-size analysis of pharmacologic treatments for generalized anxiety disorder
Hidalgo, R. B., Tupler, L. A., & Davidson, J. R. T. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881107076996 · Cited by 178 · cited 1× · see citing works
“tive in treating GAD for up to 8-weeks [29], in addition to treating SAD in those who failed to respond to sertraline [30].”
MethodBandelow, B., Allgulander, C., Baldwin, D. S., Costa, D. L. D. C., Denys, D., Dilbaz, N., Domschke, K., Eriksson, E., Fineberg, N. A., Hättenschwiler, J., et al. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2022.2086295 · Cited by 158 · cited 7× · see citing works
“One further trial concerning PTSD outpatients is ongoing (NCT04951076).”
BackgroundInfluentialTreatment-refractory anxiety; definition, risk factors, and treatment challenges
Roy‐Byrne, P. (2015) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2015.17.2/proybyrne · Cited by 151 · cited 1× · see citing works
“length of trial) or inappropriate use (contrary to evidence-based guidelines) of the treatments are certainly key factors [35].”
BackgroundCorrelates of Quality of Life in Anxiety Disorders: Review of Recent Research
Wilmer, M. T., Anderson, K., & Reynolds, M. (2021) · Current Psychiatry Reports · doi:10.1007/s11920-021-01290-4 · Cited by 150 · cited 1× · see citing works
“[11], and debilitating [12] psychiatric disorder characterized by ‘anxiety that is generalized and persistent but not restricted to, or even strongly predominating in, any particular environmental circumstances’ [13].”
BackgroundFunctional interplay between central and autonomic nervous systems in human fear conditioning
Battaglia, S., & Thayer, J. F. (2022) · Trends in Neurosciences · doi:10.1016/j.tins.2022.04.003 · Cited by 111 · cited 1× · see citing works
“Indeed one of the most common physiological symptoms, heart rate abnormalities, appears to be a driving force behind the conditioning of fear-related behaviors [2,3].”
BackgroundAktar, E., Nikolić, M., & Bögels, S. M. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.2/eaktar · Cited by 91 · cited 1× · see citing works
“transmission from parent to child [15].”
Mineur, Y. S., Fote, G. M., Blakeman, S., Cahuzac, E. L. M., Newbold, S. A., & Picciotto, M. R. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.316 · Cited by 90 · cited 1× · see citing works
“Antagonism of the α(7) nAChR, of which there is a high concentration in the rat amygdala [41], has been linked to fear-related behavior [42].”
BackgroundGregorio, D. D., Inserra, A., Enns, J. P., Markopoulos, A., Pileggi, M., Rahimy, Y. E., López-Canul, M., Comai, S., & Gobbi, G. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-022-01301-9 · Cited by 88 · cited 1× · see citing works
“as possible treatments for anxiety alongside their use in depression, with one pre-clinical Lysergic acid diethylamide study indicating efficacy [48].”
BackgroundBrain activation during anticipatory anxiety in social anxiety disorder
Boehme, S., Ritter, V., Tefikow, S., Stangier, U., Strauss, B. M., Miltner, W. H. R., & Straube, T. (2013) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nst129 · Cited by 86 · see citing works
Bandelow, B., Allgulander, C., Baldwin, D. S., Costa, D. L. D. C., Denys, D., Dilbaz, N., Domschke, K., Hollander, E., Kasper, S., Möller, H.-J., et al. (2023) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2022.2086296 · Cited by 84 · cited 7× · see citing works
“One further trial concerning PTSD outpatients is ongoing (NCT04951076).”
BackgroundInfluentialEtkin, A., Egner, T., Peraza, D. M., Kandel, E. R., & Joy Hirsch, C. (2006) · Neuron · doi:10.1016/j.neuron.2006.12.003 · Cited by 84 · see citing works
Characterizing cardiac autonomic dynamics of fear learning in humans
Battaglia, S., Orsolini, S., Borgomaneri, S., Barbieri, R., Diciotti, S., & di Pellegrino, G. (2022) · Psychophysiology · doi:10.1111/psyp.14122 · Cited by 82 · cited 1× · see citing works
“Indeed one of the most common physiological symptoms, heart rate abnormalities, appears to be a driving force behind the conditioning of fear-related behaviors [2,3].”
BackgroundPollack, M. H., Ameringen, M. V., Simon, N. M., Worthington, J. W., Hoge, E. A., Keshaviah, A. P., & Stein, M. B. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.12101353 · Cited by 78 · cited 1× · see citing works
“tive in treating GAD for up to 8-weeks [29], in addition to treating SAD in those who failed to respond to sertraline [30].”
MethodDeakin, J. F. W. (1991) · International Clinical Psychopharmacology · doi:10.1097/00004850-199112003-00002 · Cited by 70 · cited 1× · see citing works
“altered serotonergic projections from the raphe nuclei [7] and prefrontonal-limbic pathways [8] (see”
BackgroundRecent advances in the study of the comorbidity of depressive and anxiety disorders
Chen, C. (2022) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/147441 · Cited by 68 · see citing works
Klein, R. C., & Yakel, J. L. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.118232 · Cited by 51 · cited 1× · see citing works
“Antagonism of the α(7) nAChR, of which there is a high concentration in the rat amygdala [41], has been linked to fear-related behavior [42].”
BackgroundFayuk, D. A., & Yakel, J. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135319 · Cited by 43 · see citing works
Perkins, A. M., Patrick, F., Wise, T., Meyer, N., Mazibuko, N., Oates, A. E., van der Bijl, A. H. M., Danjou, P., O'Connor, S. M., Doolin, E. E., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01141-5 · Cited by 36 · cited 4× · see citing works
“[22], suggest that the response to BNC210 may be hormetic, as low-dose, but not high dose,”
BackgroundInfluentialSelf-citationCholinergic Modulation of Disorder-Relevant Neural Circuits in Generalized Anxiety Disorder
Wise, T., Patrick, F., Meyer, N., Mazibuko, N., Oates, A. E., van der Bijl, A. H. M., Danjou, P., O'Connor, S. M., Doolin, E. E., Wooldridge, C., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.12.013 · Cited by 31 · cited 5× · see citing works
“Wise and colleagues [21] administered BNC210 to 24 adults with GAD, returning that lowdose BNC210 reduced amygdalar reactivity to fearful faces at a”
BackgroundMethodInfluentialSelf-citationArias, H. R., Targowska‐Duda, K. M., García‐Colunga, J., & Ortells, M. O. (2021) · Molecules · doi:10.3390/molecules26082149 · Cited by 30 · cited 1× · see citing works
“SSRIs have been shown to inhibit nicotinic acetylcholine receptors, suggesting that SSRIs may act via cholinergic, alongside serotonergic, modulation [43].”
BackgroundHeritability of social anxiety disorder: a systematic review of methodological designs
Moreno, A. L., Osório, F. D. L., Martin-Santos, R., & Crippa, J. A. D. S. (2016) · Archives of Clinical Psychiatry (São Paulo) · doi:10.1590/0101-60830000000090 · Cited by 11 · cited 1× · see citing works
“Although estimates regarding the heritability of SAD vary in the literature, reported from 13–76% [19], there is a significant, but not exclusive, genetic component to SAD.”
BackgroundBenzodiazepine Site Agonists Differentially Alter Acetylcholine Release in Rat Amygdala
Hambrecht‐Wiedbusch, V. S., Mitchell, M. F., Firn, K. A., Baghdoyan, H. A., & Lydic, R. (2014) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000000201 · Cited by 9 · cited 1× · see citing works
“Although not shown in humans, rat models have demonstrated cholinergic inhibition of amygdalar activity following benzodiazepine administration [44], leaving open”
BackgroundInfluentialBallenger, J. C. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00304-7 · Cited by 4 · cited 1× · see citing works
“Taken together, roughly 50% of patients show a response to the above treatments, with only a third achieving remission [34].”
BackgroundO'Connor, S., Andriambeloson, E., Huyard, B., Wagner, S., Sleebs, B. E., Bui, C., Kremmidiotis, G., Street, I., & Flynn, B. L. (2008) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(08)70741-7 · Cited by 4 · see citing works
Kremmidiotis, G., Doolin, E. E., Metzger, D., Drutinus, E., Danjou, P., & O'Connor, S. (2011) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(11)70859-8 · Cited by 3 · cited 2× · see citing works
“headache) in a small number of participants [46,47].”
BackgroundGiles, J. (2004) · Nature · doi:10.1038/news041025-8 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Tae, H., Ortells, M. O., Tekarli, B., Manetti, D., Romanelli, M. N., McIntosh, J. M., Adams, D. J., & Arias, H. R. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.3c00212 · Cited by 14 · see citing works
Papapetropoulos, S., Doolin, E. E., Odontiadis, M., Paul, D., Jaros, M. J., Rolan, P. E., Taylor, C. T., & Stein, M. B. (2025) · Psychiatry Research · doi:10.1016/j.psychres.2025.116387 · Cited by 7 · see citing works
BNC210, an α7 Nicotinic Receptor Modulator, in Post-Traumatic Stress Disorder
Papapetropoulos, S., Doolin, E., O’Connor, S., Paul, D., Odontiadis, M., Jaros, M., Rolan, P., & Stein, M. B. (2025) · NEJM Evidence · doi:10.1056/evidoa2400380 · Cited by 5 · see citing works
Kini, R. M., & Koh, C. Y. (2025) · Toxins · doi:10.3390/toxins17080364 · Cited by 8 · see citing works
He, Y., Polymeropoulos, C. M., Mohrman, M. A., Truslow, S. O., Xiao, C., Wu, Y., Birznieks, G., & Polymeropoulos, M. H. (2025) · The British Journal of Psychiatry · doi:10.1192/bjp.2025.84 · Cited by 5 · see citing works
“36 Interestingly, BNC210, an α 7-nAChR negative-allosteric modulator, also showed anxiolytic effect in patients with generalised anxiety disorder.”
Rolan, P., Doolin, E., Paul, D., Crossman, J., Odontiadis, M., Danjou, P., Smith, M., & Papapetropoulos, S. (2026) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.1609 · Cited by 3 · see citing works
GABA System in Anxiety Disorders: A Review of Current and Novel GABAergic Drugs
Cai, Y., & Xu, E. (2023) · Journal of Education Humanities and Social Sciences · doi:10.54097/ehss.v22i.12411
“Find the latent side effects [25].”
Baldwin, D. S., & Huneke, N. T. M. (2025) · The British Journal of Psychiatry · doi:10.1192/bjp.2025.10368
Linfang, W., & Yang, L. (2025) · Brain and Behavior · doi:10.1002/brb3.71095
“While medicationhasbeenshowntobeeffectiveforadolescenceanxiety disorders (Mills et al. 2024), limitations exist regarding drug types (Nicotra and Strawn 2023), safety (Hampsey et al. 2023), long-term effects (Kim et al. 2023), and potential dependency (Hampsey et al. 2023).”
- Authors
- Hampsey, E., Perkins, A., & Young, A. H.
- Affiliations
- King's College London (GB)
- Corresponding author
- Hampsey, Elliot
- Venue
- Expert Opinion on Investigational Drugs
- Publisher
- Informa UK Limited
- Published
- 2023-03-20
- Volume
- 32
- Issue
- 4
- Pages
- 277-282
- ISSN
- 1354-3784 (ISSN-L)
- 1744-7658
- OpenAlex
- W4327547028
- Cited by
- 9
- References
- 44
- Citations by year
- 2025: 6 · 2024: 1 · 2023: 2
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Expert Opinion on Investigational Drugs (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Portal (King's College London) (acceptedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- alpha7 nicotinic acetylcholine receptor, negative allosteric modulators, anxiety disorders, anxiolytics, social anxiety disorder, post-traumatic stress disorder, pharmacodynamics, pharmacokinetics, mechanism of action, neural circuits
- MeSH terms
- Aged, Anxiety Disorders, Humans, Anti-Anxiety Agents, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
