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

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.

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.

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.

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.