Safety, tolerability, pharmacokinetic and pharmacodynamic effects of the muscarinic M₁ positive allosteric modulator VU0467319 for Alzheimer's disease: a single ascending-dose study in healthy participants.

ABSTRACT: The development of cholinergic neurotransmitter based cognitive enhancers for Alzheimer's disease and other neuropsychiatric disorders have focused recently on allosteric modulation of specific muscarinic acetylcholine receptor (mAChR) subtypes to reduce dose-limiting side-effects that have been the hallmark of earlier orthosteric mAChR agonists. VU0467319 (VU319) is an investigational positive allosteric modulator of the M₁ mAChR. A Phase 1 first-in-human study was conducted assessing safety and brain activity utilizing cognitive tasks and event-related potentials (ERPs) in single-ascending dose and food effect studies. VU319 was given orally to 52 healthy volunteers aged 18-55 years. The single ascending dose study tested 40 participants in five dose escalating cohorts (60, 12

SUBMITTER: Conley AC 

PROVIDER: S-EPMC12211128 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature