Icopezil (maleate)

Icopezil maleate (CP-118954 maleate) is an orally active, selective AchE inhibitor with an IC₅₀ of 0.33 nM. Icopezil maleate increases acetylcholine levels in the brain and striatum of mammals, induces centrally mediated tremors and peripherally mediated salivation, and improves working memory performance in aged dogs. Icopezil maleate serves as a parent compound for radioiodine-labeled acetylcholinesterase imaging agents. Icopezil maleate is applicable to research related to Alzheimer's disease^[1][2][3][4]. In Vitro:Icopezil (15 min) maleate potently and selectively inhibits acetylcholinesterase in vitro (IC₅₀ = 0.33 nM), with an inhibitory activity far stronger than that against human butyrylcholinesterase (IC₅₀ = 7200 nM)^[1].
Icopezil maleate exhibits no significant in vitro activity against a variety of central nervous system-related receptors and enzymes (IC₅₀ > 1 μM)^[1].
Icopezil maleate is a sub-nanomolar acetylcholinesterase (AChE) inhibitor with over 10000-fold selectivity for butyrylcholinesterase (BChE)^[3].
Icopezil maleate potently inhibits erythrocyte acetylcholinesterase, with an IC₅₀ of 0.33 nM, and exhibits much higher selectivity for AChE than for BuChE^[4]. In Vivo:Icopezil maleate (0.32-32 mg/kg; p.o.) dose-dependently increases acetylcholine levels in the brains of mice, reaching 200% of the control level at the oral dose of 32 mg/kg; its therapeutic index is superior to that of non-selective cholinesterase inhibitors, and its potency to induce central tremors is three times that to induce peripheral salivation^[1].
Co-administration of Icopezil (1-10 mg/kg; p.o.) maleate with iso-OMPA (HY-131922) enhances its peripheral salivary secretion response and acute lethality in mice^[1].
Icopezil maleate (0.02-0.12 mg/kg; p.o.) exerts only mild, statistically insignificant cognitive-enhancing effects in aged male Beagle dogs^[2].