What is the mechanism of action (MOA) of homatropine?

Mechanism of Action of Homatropine

Homatropine is an anticholinergic agent that competitively blocks muscarinic acetylcholine receptors, preventing acetylcholine from binding and thereby inhibiting parasympathetic nervous system activity. 1

Pharmacological Classification

• Homatropine hydrobromide is classified as an anticholinergic/antimuscarinic agent prepared as a sterile topical ophthalmic solution 1
• It functions as a muscarinic receptor antagonist, similar in mechanism to atropine but with different potency and duration characteristics 2

Molecular Mechanism

• Homatropine competitively inhibits acetylcholine at postganglionic muscarinic receptor sites, preventing the normal parasympathetic neurotransmitter from activating these receptors 2
• The drug binds to muscarinic acetylcholine receptors (mAChRs), which are widely distributed in both peripheral and central nervous systems for regulation of cholinergic functions 2
• This competitive antagonism blocks the parasympathetic effects that would normally be mediated through acetylcholine binding 2

Clinical Effects from Muscarinic Blockade

When applied topically to the eye, homatropine's antimuscarinic action produces:

• Mydriasis (pupil dilation) by blocking parasympathetic innervation to the iris sphincter muscle 3
• Cycloplegia (paralysis of accommodation) by blocking parasympathetic control of the ciliary muscle 3
• These effects occur because muscarinic receptors in the eye normally mediate pupil constriction and lens accommodation 3

Systemic Absorption Considerations

• Despite topical ophthalmic administration, homatropine can be systemically absorbed and cause anticholinergic effects throughout the body 3
• Systemic absorption can lead to central anticholinergic toxicity, including metabolic delirium, as confirmed by muscarinic radioreceptor assays 3
• The anticholinergic effects extend beyond the eye when sufficient systemic levels are achieved 3

Comparison to Atropine

• Both homatropine and atropine are muscarinic receptor antagonists with similar mechanisms of action 2, 4
• Homatropine at 20 mg/kg demonstrated comparable efficacy to atropine 10 mg/kg in preventing lethality in organophosphate poisoning models, suggesting similar antimuscarinic potency at appropriate doses 4
• The primary differences lie in potency, duration of action, and receptor subtype selectivity rather than fundamental mechanism 2, 4

Interaction with Choroidal Regulation

• Homatropine's muscarinic blockade appears to prevent choroidal thinning responses to hyperopic defocus, suggesting muscarinic pathways are involved in choroidal thickness regulation 5
• The drug blocks the eye's normal choroidal thinning response to imposed hyperopic blur, indicating muscarinic receptors mediate this adaptive response 5