1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)
blankLoading...

5-HT Receptor Modulators

Overview

5-HT Receptor ModulatorsClinical research has shown that modulation of 5-HT3 and 5-HT4 receptors affects visceral pain sensation and intestinal transit. The serotonin (5-HT) receptor modulator drug class has received the majority of irritable bowel syndrome researchers’ attention for nearly a decade.

However, early agents in this class — alosetron (GlaxoSmithKline’s Lotronex) and tegaserod (Novartis’s Zelnorm/Zelmac) — have encountered considerable opposition during the approval process as a result of safety concerns revealed during clinical trials and postmarketing studies. These agents have been approved in the United States, but their prescription (particularly prescription of alosetron) is tightly regulated.

In addition, because 5-HT receptor modulators have specificity for a single motility symptom (either diarrhea or constipation), more than 50% of the irritable bowel syndrome population is necessarily excluded from treatment with any given 5-HT modulator.

The challenge for emerging agents within this class is to demonstrate significant improvements in both efficacy and safety over existing agents to gain wider approval. Several companies are pursuing 5-HT receptor modulators for the treatment of irritable bowel syndrome. GlaxoSmithKline (GSK), Mitsubishi-Tokyo Pharma, Pharmagene, and Meiji Seika Kaisha have discovery-phase programs, while Solvay, Alizyme, and Eisai have agents in later-stage development.

Mechanism Of Action

Agents in the 5-HT receptor modulator class stimulate or inhibit the activity of 5-HT receptors in the gut, reducing visceral pain sensations and altering intestinal transit in irritable bowel syndrome patients.

TABLE : Emerging Therapies in Development for Irritable Bowel Syndrome

Compound Development Phase Marketing Company
5-HT receptor modulators    
Cilansetron      
United States D Solvay  
Europe III Solvay  
Japan  
Renzapride      
United States II Alizyme  
Europe II Alizyme  
Japan  
E-3620      
United States  
Europe  
Japan II Eisai  
Tachykinin receptor antagonists    
Nepadutant      
United States  
Europe II Menarini  
Japan  
Saredutant      
United States  
Europe II Sanofi-Synthelabo  
Japan  
Talnetant      
United States  
Europe II GlaxoSmithKline  
Japan  
Cholecystokinin A receptor antagonists    
Dexloxiglumide      
United States D Forest Laboratories/RottaPharm  
Europe III RottaPharm  
Japan  
Opioid receptor modulators    
PTI-901      
United States D Pain Therapeutics  
Europe  
Japan  
Asimadoline      
United States  
Europe II Merck KGaA  
Japan  
Corticotrophin-releasing factor receptor antagonists  
NBI-34041      
United States  
Europe I Neurocrine Biosciences  
Japan  
Chloride-channel activators    
SPI-0211 (RU-0211)      
United States II Sucampo Pharmaceuticals  
Europe  
Japan  

D = Discontinued.

Cilansetron

Renzapride

E-3620

Eisai is developing E-3620, an agent in Phase II clinical trials in Japan for irritable bowel syndrome, gastric motility disorders, and gastritis. Like renzapride, E-3620 is a dual 5-HT3 antagonist/5-HT4 agonist. In 1999, the company reported that treatment with E-3620 is associated with an improvement in the symptoms of diarrhea and the sense of fullness and anorexia associated with chronic gastritis and irritable bowel syndrome.

Leave a Reply

  Subscribe  
Notify of