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Molecular and structural insights into the serotonin 5-HT2C receptor as a therapeutic target for substance use disorders
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  • Maleesha Ubhayarathna,
  • Chris Langmead,
  • Natalie Diepenhorst,
  • Gregory Stewart
Maleesha Ubhayarathna
Monash Institute of Pharmaceutical Sciences Drug Discovery Biology

Corresponding Author:[email protected]

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Chris Langmead
Monash Institute of Pharmaceutical Sciences Drug Discovery Biology
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Natalie Diepenhorst
Monash Institute of Pharmaceutical Sciences
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Gregory Stewart
Monash Institute of Pharmaceutical Sciences Drug Discovery Biology
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Abstract

Substance use disorder (SUD) is a chronic condition with maintained abuse of a substance leading to physiological and psychological alterations and often changes in cognitive and social behaviours. Current therapies mainly consist of psychotherapy coupled with medication; however, alarmingly high relapse rates reveal the shortcomings of the current standard of care. The signalling and expression profile, and neurological function of the serotonin 2C receptor (5-HT2C receptor) make it an ideal candidate of interest for the treatment of SUD. This is further corroborated by pre-clinical and clinical evidence of therapeutically relevant compounds acting at the 5-HT2C receptor. Notwithstanding, drug binding at closely related serotonin receptor subtypes has impeded drug development. More recently, psychedelics, which broadly act at 5-HT2 receptors, have indicated promising potential for the treatment of SUD, implicating in part, the 5-HT2C receptor. The modern psychedelic movement has rekindled therapeutic interest in the 5-HT2C receptor, resulting in an influx of new studies, especially structural analyses. This review delves into the structural, molecular and cellular mechanisms governing the 5-HT2C receptor function, in the context of SUD. This provides the basis of the preclinical and clinical evidence for their role in SUD and highlights the potential for future exploration.
31 Oct 2022Submitted to British Journal of Pharmacology
08 Nov 2022Submission Checks Completed
08 Nov 2022Assigned to Editor
09 Nov 2022Reviewer(s) Assigned
27 Nov 2022Review(s) Completed, Editorial Evaluation Pending
28 Nov 2022Editorial Decision: Revise Minor
22 May 20231st Revision Received
22 May 2023Submission Checks Completed
22 May 2023Assigned to Editor
22 May 2023Review(s) Completed, Editorial Evaluation Pending
23 May 2023Editorial Decision: Revise Minor
02 Aug 20232nd Revision Received
08 Aug 2023Submission Checks Completed
08 Aug 2023Assigned to Editor
09 Aug 2023Review(s) Completed, Editorial Evaluation Pending
09 Aug 2023Editorial Decision: Accept