Alzheimer’s Disease Therapy

Cholinesterase Inhibitors:
1. Tacrine (Tetrahydroaminoacridine) – long acting cholinesterase inhibitor and muscarinic modulator, it has
hepatic toxicity, so it is not used and replaced by others.
2. Donepezil, Rivastigmine and Galantamine:
a. Pharamcokinetics - Orally active agents, penetrate CNS and less toxic. Metabolized by CYP450, risk for
drug interactions with azoles and quinidine.
b. Side Effects – nausea, vomiting, diarrhea, bradycardia, hypotension, sweating, salivation, anxiety,
ataxia.
c. Indication - The drug doesn’t prevent the disease progression, and it is recommended in mild-moderate
AD.

NMDA Inhibitors:
Memantine – binds NDMA receptor channels in a use-dependent manner  non-competitive blockade.
1. Indication – mild-moderate AD, with modest effect like Cholinesterase Inhibitors.
2. Side Effect – better tolerated, less toxic.

Anti-Amyloid Beta:
Verubecestat – inhibitor of beta site amyloid precursor protein cleaving enzyme (BACE1)  reduce the
production of beta-amyloid. It is in clinical trials.