Idalopirdine vs Masupirdine

Idalopirdine is a potent, selective serotonin 5-HT6 receptor antagonist developed by H. Lundbeck (as Lu AE58054) as an adjunctive symptomatic treatment for Alzheimer's disease. By blocking 5-HT6 receptors, which are expressed almost exclusively in the central nervous system and concentrated in the hippocampus and cortex, it disinhibits cholinergic, glutamatergic and monoaminergic transmission relevant to memory. A phase 2 trial (LADDER) in donepezil-treated moderate Alzheimer's disease showed a significant cognitive benefit, but the larger phase 3 STARSHINE, STARBEAM and STARBRIGHT programme failed to replicate it. Idalopirdine is discontinued for cognition and is now referenced primarily as a pharmacological tool and cautionary case study.

effects

Serotonin, Acetylcholine, Glutamate, GABA

targets

5-HT6 receptor, GABAergic interneurons, Cholinergic system, Appetite / metabolic regulation

evidence

Moderate clinical data; positive phase 2, negative phase 3

suppliers

reference only

Masupirdine is a potent, selective serotonin 5-HT6 receptor antagonist developed by Suven Life Sciences as SUVN-502 for cognitive deficits in Alzheimer's disease. It was distinctive as the first compound in its class tested on a background of both donepezil and memantine, reflecting real-world moderate Alzheimer's disease management. The pivotal phase 2 proof-of-concept study did not meet its prespecified cognitive endpoint, although exploratory post hoc analyses suggested that concurrent memantine may have masked a benefit. Suven has since pivoted masupirdine toward agitation in dementia rather than core cognition.

effects

Serotonin, Acetylcholine, Glutamate, GABA

targets

5-HT6 receptor, Cholinergic system, Glutamatergic circuits, Behavioural / mood circuits

suppliers

reference only