Intepirdine vs Masupirdine

Intepirdine is a selective serotonin 5-HT6 receptor antagonist originally discovered at GlaxoSmithKline as SB-742457 and later licensed to Axovant Sciences as RVT-101 for Alzheimer's disease and dementia with Lewy bodies. Like other compounds in its class it was intended to enhance cognition by disinhibiting cholinergic and glutamatergic signaling in cortex and hippocampus. A phase 2 study suggested a modest global and cognitive benefit, but the pivotal phase 3 MINDSET trial in mild-to-moderate Alzheimer's disease was clearly negative. Its high-profile failure in 2017 effectively ended enthusiasm for 5-HT6 antagonism as a standalone dementia strategy.

effects

Serotonin, Acetylcholine, Glutamate, GABA

targets

5-HT6 receptor, Cortical GABA interneurons, Cholinergic system

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