Mechanism of Action

Ladostigil is composed of a Carbamate moiety which is a known acetyl cholinesterase / butyryl cholinesterase inhibitor; and a Propargyline moiety, which is a selective monoamine oxidase B inhibitor with neuro-protective (anti-apoptotic and anti-inflammatory) properties. As such, its mechanism of action is probably multi-faceted and complex.

In low doses (non-enzyme-inhibitory) it is thought that the primary mechanism of action involves Preventing or delaying cognitive impairment and acting as a disease modifying agent by neuro-protection, immune modulation and reduction of oxidative stress.

Signs of oxidative stress (oxidized lipids, DNA, and proteins) are known to be found in brains of MCI subjects1. This oxidative stress triggers microglial activation, which can be detected by PET imaging with ligand 11CPK 111952. The activated microglia produce pro-inflammatory cytokines, including TNF-α, IL-1β, and NO.

MOA1

When stress is induced on mouse brains by LPS, Ladostigil was shown to reduce levels of Cytokines, Oxidative Stress, Galectin 3 and COX.

MOA2

 

1. Keller et al, Neurology 2009

2. Okello et al, Neurology 2009