Clinical Update of Velnacrine Research

Abstract

Velnacrine is a 1,2,3,4-tetrahydro-9-aminoacridine-1-ol maleate which acts biochemically as a potent cholinesterase inhibitor (ChEI). Due to its ability to enhance cholinergic functions, it has been developed as an Alzheimer’s disease (AD) agent. Pharmacological studies in rodents demonstrated that the compound can improve learning and memory functions and reverse learning deficits caused either by scopolamine or lesions of the nucleus basalis magnocellularis (NBM) (which in rats is the equivalent of the nucleus basalis of Meynert complex in man) (Fielding et al., 1989). In pharmacokinetic studies in humans, plasma peak levels were reached within one hr after oral administration, and the drug was rapidly eliminated with a half-life of about two to three hrs. Steady-state plasma levels were reached after approximately three days of repeated dose (t.i.d.) treatment. There were dose-related increases in peak plasma concentrations (Cmax), areas under the plasma concentration — time curves (AUC) and the amount of drug excreted in the urine (Puri et al., 1988). Results from a food interaction study suggest that food may delay time to peak concentration and reduce Cmax, but not significantly alter the amount of absorbed substance.