Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures
N. R. Cutler, J. Haxby, A. D. Kay, P. K. Narang, L. J. Lesko, J. L. Costa, M. Ninos, M. Linnoila, W. Z. Potter, J. W. Renfrew and al. et
Neuropsychological and neurochemical effects of zimeldine, a relatively
specific serotonin reuptake blocker, were examined in four patients with
clinically diagnosed Alzheimer's disease, in a double-blind,
placebo-controlled, crossover study. Individualized doses of zimeldine were
administered to achieve target plasma zimeldine concentrations of
approximately 50 (low) to 100 (high) ng/mL. Overall, there was no
significant effect of zimeldine on memory or reaction time measures as
compared with placebo. The drug significantly reduced (by up to 38%)
5-hydroxyindoleacetic acid concentrations in the cereobrospinal fluid and
almost abolished (90% reduction) platelet serotonin uptake. Cerebrospinal
fluid concentrations of 3-methoxy-4-hydroxy-phenylglycol, a major
metabolite of norepinephrine, and homovanillic acid, the major metabolite
of dopamine, were not altered. Our findings indicate that alterations in
central and peripheral serotoninergic function by a serotonin reuptake
blocker (zimeldine) are unaccompanied by measurable changes in memory
and/or reaction time in patients presumed to have Alzheimer's disease.
