What is the mechanism of action of Levocloperastine?

Mechanism of Action of Levocloperastine

Levocloperastine is a peripherally-acting antitussive agent that works by inhibiting pulmonary afferent activity and activating C-fiber sensory afferents that reflexively inhibit cough. 1

Primary Mechanism

Levocloperastine belongs to the class of peripherally-acting cough suppressants. These medications work primarily through:

1. Direct action on sensory elements in the respiratory tract:

   • Inhibits pulmonary afferent nerve activity that triggers the cough reflex 1
   • Acts on peripheral receptors in the tracheobronchial tree 2

2. Reflexive inhibition of cough:

   • Activates C-fiber sensory afferents that provide inhibitory feedback to the cough center 1

Advantages Over Central Antitussives

Unlike centrally-acting antitussives (such as opioids), levocloperastine:

• Does not penetrate the central nervous system (CNS) to an appreciable extent 1
• Does not cause sedation or other central side effects commonly associated with opioids 2
• Does not depress respiratory center output or affect ventilatory responses to hypercapnia 3

A randomized clinical trial demonstrated that levocloperastine, unlike dihydrocodeine (an opioid antitussive), did not affect respiratory responses to CO2 rebreathing tests in patients with chronic cough, confirming its peripheral mechanism of action 3.

Clinical Applications

Levocloperastine is recommended as a third-line peripherally-acting antitussive for:

• Opioid-resistant cough in lung cancer patients 1
• Management of chronic nonproductive cough 2
• Treatment of dry cough in adults 4

The American College of Chest Physicians guidelines suggest using peripherally-acting antitussives like levocloperastine when cough does not respond to opioid derivatives, particularly in lung cancer patients 1.

Efficacy

Clinical studies have shown that levocloperastine:

• Significantly improves cough symptoms (intensity and frequency) with improvements observed after the first day of treatment 2
• Reduces nighttime awakenings and irritability in children 2
• Has comparable or improved efficacy compared to other antitussive agents, with a more rapid onset of action 2
• Effectively reduces cough severity, frequency, and sleep disruption with improvement in quality of life 4

Dosing

The recommended dosage for levocloperastine is 20 mg three times daily (tid) 1.

Important Considerations

• If a short course of treatment does not lead to improvements, the treatment should be discontinued and another approach tried 1, 5
• Levocloperastine is not approved for use in the United States 1
• No evidence of central adverse events has been recorded with levocloperastine, making it a safer alternative to centrally-acting antitussives 2

The peripheral mechanism of action of levocloperastine makes it particularly valuable in situations where respiratory depression must be avoided, such as in patients with respiratory insufficiency or those at risk for CNS depression.