A Clonidine‐Associated α‐Adrenergic Hypothesis in Sleep Bruxism Pharmacotherapy: An Evidence‐Anchored Target Analysis

Abstract

ABSTRACT Background Sleep bruxism (SB) is a centrally regulated, arousal‐related motor behaviour, but no pharmacotherapy has demonstrated reliable clinical efficacy. This study aimed to identify pathway‐level signals most consistently supported by current polysomnography (PSG)‐based pharmacotherapy evidence for SB. Methods We performed an evidence‐anchored bioinformatic analysis of six drugs evaluated in randomized or controlled. Drugs were classified as effective or not‐supported according to prespecified clinical efficacy criteria. Human pharmacodynamic targets were curated from GtoPdb and DrugBank, with precursor‐derived metabolite targets excluded. Target convergence and Effective‐versus‐Not‐supported contrasts were assessed using enrichment analyses with sensitivity testing across drug classification, enrichment background and retention thresholds. Results Thirty‐one curated pharmacodynamic targets converged on monoaminergic and GABA‐A receptor systems, including adrenergic, dopaminergic, serotonergic and GABA‐A receptor signalling. The Effective‐versus‐Not‐supported contrast retained 14 Effective‐side terms, all driven by α‐adrenergic receptors (ADRA1A/1B/1D and ADRA2A/2B/2C). Dopamine‐receptor enrichment was present in the broader target profile but was not retained in the efficacy contrast. Precursor‐aware curation further showed that levodopa contributed to GPR143 rather than direct dopamine‐receptor targets. Conclusions This efficacy‐anchored analysis generated a clonidine‐associated α‐adrenergic, arousal‐related pharmacological signal within the limited available evidence. The findings are more consistent with a central arousal‐related hypothesis for SB pharmacotherapy than with a single motor‐target or dopamine‐driven treatment model, but require confirmation in contemporary PSG‐based clinical studies and real‐world patient populations.

The authors' abstract, as published at the source. Journal of Oral Rehabilitation, 2026 · DOI ↗