BNC210: an investigational α7-nicotinic acetylcholine receptor modulator for the treatment of anxiety disorders

ABSTRACT

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 BNC210ʹs 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.

KEYWORDS:

• Anxiety disorders
• social anxiety disorder
• anxiolytic
• nicotinic acetylcholine receptor
• BNC210
• non-sedating

Article highlights

• The article first discusses recommended pharmacological treatment options in anxiety disorders, followed by the potential role of cholinergic system in fear-related behaviors.

• The article then overviews BNC210; a novel anxiolytic currently under development. This includes a status update regarding the development of BNC210 and rival compounds.

• The article concludes by providing an expert opinion on BNC210 and its place in the wider novel anxiolytic environment both now and in the future.

Declaration of interest

AH Young: Employed by King’s College London; Honorary Consultant South London and Maudsley NHS Foundation Trust (NHS UK)

Editor of Journal of Psychopharmacology and Deputy Editor, BJPsych Open,

Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Allegan, AstraZeneca, Bionomics Ltd, Boehringer Ingelheim, COMPASS, Eli Lilly, Janssen, LivaNova, Lundbeck, Neurocentrx, Novartis, Sage, Servier, Sumitomo Dainippon Pharma, Sunovion

Principal Investigator in the Restore-Life VNS registry study funded by LivaNova.

Principal Investigator on ESKETINTRD3004: ‘An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.’

Principal Investigator on ‘The Effects of Psilocybin on Cognitive Function in Healthy Participants’

Principal Investigator on ‘The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)’

UK Chief Investigator for Novartis MDD study MIJ821A12201

Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK) EU Horizon 2020

No shareholdings in pharmaceutical companies

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.