What is the difference between alisapride and mosapride?

Alisapride vs. Mosapride: Key Pharmacological and Clinical Differences

Alisapride and mosapride are fundamentally different prokinetic agents with distinct mechanisms of action, safety profiles, and clinical applications—alisapride is a dopamine D2 receptor antagonist (similar to metoclopramide), while mosapride is a selective 5-HT4 receptor agonist with partial 5-HT3 antagonist properties.

Mechanism of Action

Alisapride

• Acts primarily as a dopamine D2 receptor antagonist, similar to metoclopramide, which stimulates gastric emptying through dopaminergic blockade 1
• Carries significant risk of extrapyramidal side effects and tardive dyskinesia due to D2 receptor blockade, particularly with long-term use 1

Mosapride

• Selective 5-HT4 receptor agonist that facilitates acetylcholine release from enteric cholinergic neurons 2, 3
• Partial 5-HT3 antagonist through its main metabolite M1, providing additional antiemetic properties 4
• Does not block dopamine D2 receptors, eliminating the risk of extrapyramidal symptoms 3
• Does not prolong QT interval or cause cardiac arrhythmias, unlike cisapride 3

Clinical Efficacy

Mosapride's Proven Benefits

• Enhances gastric emptying with potency equal to cisapride and superior to metoclopramide in animal models 3
• Reduces esophageal acid exposure by decreasing total reflux episodes, episodes lasting >5 minutes, and improving acid clearance time in GERD patients 4
• Improves constipation in Parkinsonian patients by shortening colonic transit time and augmenting rectal contractions 2
• Effective for functional dyspepsia, particularly postprandial distress syndrome, though guidelines note mosapride is available in Asia 5

Comparative Efficacy Data

• In head-to-head trials, itopride showed superior efficacy to mosapride (93.3% vs 63.3% excellent-to-good response) for functional dyspepsia 6
• Acotiamide demonstrated similar efficacy to mosapride (98% vs 93.27% responder rate) with comparable safety profiles 7

Safety Profile

Alisapride Safety Concerns

• High risk of extrapyramidal side effects including potentially irreversible tardive dyskinesia, especially in elderly patients 1
• Not recommended for long-term use due to neurological adverse effects 1

Mosapride Safety Advantages

• Well-tolerated with minimal side effects—only 1 of 14 patients discontinued due to epigastric discomfort in Parkinsonian study 2
• No worsening of parkinsonism or extrapyramidal symptoms 2
• No cardiac effects such as QT prolongation or torsades de pointes 3
• Adverse event rate of 16.7% in one study, with only 6.7% requiring discontinuation 6

Clinical Positioning

When to Avoid D2 Antagonists (Like Alisapride)

• Elderly patients at higher risk for tardive dyskinesia 1
• Parkinsonian patients where D2 blockade could worsen motor symptoms 2
• Patients requiring long-term therapy due to cumulative neurological risk 1
• Patients with cardiac risk factors if considering older agents like cisapride 3

Mosapride's Clinical Niche

• First-line prokinetic for dysmotility-like symptoms (fullness, bloating, early satiety) in functional dyspepsia 5, 8
• GERD management when combined with acid suppression therapy 5, 4
• Constipation in special populations including Parkinsonian patients 2
• Preferred in Asia where it is widely available alongside itopride and domperidone 5

Critical Clinical Caveat

The fundamental difference is safety: mosapride's selective 5-HT4 agonism without D2 blockade eliminates the neurological risks inherent to alisapride and similar dopamine antagonists, making mosapride the safer choice for most clinical scenarios requiring prokinetic therapy 3. However, neither agent is universally available—mosapride is primarily used in Asia, while alisapride has limited global distribution 5.