TAK-906, a D2/D3 receptor antagonist developed by Altos Therapeutics and Takeda, is being investigated as a treatment for gastroparesis. This peripherally-restricted molecule is designed to avoid penetration of the blood-brain barrier, focusing its activity on the stomach and the vomiting center located in the area postrema.
Gastroparesis and the Role of D2/D3 Receptors
Gastroparesis is a chronic condition characterized by delayed gastric emptying, leading to a range of debilitating symptoms. These include nausea, vomiting, abdominal pain, and anorexia. The pathophysiology of gastroparesis involves dysregulation of gastric motility, and dopamine receptors, particularly D2 and D3 subtypes, play a significant role in modulating gastrointestinal function. By antagonizing these receptors peripherally, TAK-906 aims to enhance gastric emptying and reduce associated symptoms.
Mechanism of Action and Therapeutic Potential
TAK-906's mechanism of action involves selective antagonism of D2 and D3 receptors in the gastrointestinal tract. Unlike centrally acting dopamine antagonists, TAK-906 is designed to minimize central nervous system side effects due to its limited ability to cross the blood-brain barrier. This targeted approach could offer a significant advantage in managing gastroparesis, providing symptomatic relief without the neurological complications associated with other dopamine-blocking agents. The drug targets the stomach and vomiting center in the area postrema to treat gastroparesis.
