Mechanism of Action of Topical Glycopyrrolate in Treating Hyperhidrosis
Topical glycopyrrolate works by blocking acetylcholine receptors on sweat glands, preventing the activation of these glands and thereby reducing sweat production. 1
Pharmacological Mechanism
Glycopyrrolate is an anticholinergic (antimuscarinic) agent that:
- Inhibits the action of acetylcholine on structures innervated by postganglionic cholinergic nerves 1
- Acts on smooth muscles that respond to acetylcholine but lack cholinergic innervation 1
- Antagonizes muscarinic symptoms by blocking peripheral cholinergic receptors present in autonomic effector cells 1
- Has a quaternary ammonium structure that limits its passage across lipid membranes (including the blood-brain barrier), unlike tertiary amines such as atropine and scopolamine 1
Clinical Application in Hyperhidrosis
When applied topically for hyperhidrosis, glycopyrrolate:
- Reduces sweat production by blocking the activation of acetylcholine receptors specifically in peripheral sweat glands 2
- Provides a localized anticholinergic effect at the application site with minimal systemic absorption due to its quaternary structure 1
- Is effective for various types of hyperhidrosis including:
Efficacy and Formulations
- Available as pre-moistened cloths containing 2.4% glycopyrronium solution (Qbrexza™) for primary axillary hyperhidrosis 2
- Can be formulated as topical solutions of various concentrations (0.5%-2%) for facial and other forms of hyperhidrosis 6, 5
- Clinical trials have demonstrated significant reductions in both patient-reported severity of sweating and objectively measured sweat production 3
Advantages Over Other Anticholinergics
The quaternary ammonium structure of glycopyrrolate gives it distinct advantages:
- Limited passage across the blood-brain barrier, resulting in fewer central nervous system side effects 1
- More targeted action on peripheral cholinergic receptors 1
- Provides a non-invasive alternative to clinic-based treatments for adults with primary axillary hyperhidrosis 4
- Is the only FDA-approved alternative to topical antiperspirants specifically for children and adolescents ≥9 years of age with primary axillary hyperhidrosis 4
Common Side Effects
- Dry mouth (9%-41%)
- Constipation (9%-39%)
- Behavioral changes (18%-36%)
- Local skin reactions at application site 7
Topical glycopyrrolate has demonstrated efficacy with minimal systemic side effects, making it an effective treatment option for various forms of hyperhidrosis.