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Cognitive and Biochemical Measures

Neal R. Cutler, MD; James Haxby, PhD; Arthur D. Kay, MD; Prem K. Narang, PhD; Lawrence J. Lesko, PhD; Jonathan L. Costa, MD, PhD; Mary Ninos, RN, MS; Markku Linnoila, MD, PhD; William Z. Potter, MD, PhD; James W. Renfrew, MA; Angela M. Moore, MS

Arch Neurol. 1985;42(8):744-748.

Abstract
• 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-hydroxyphenylglycol, 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.

Author Affiliations
From the Section on Brain Aging and Dementia, Laboratory of Neurosciences, National Institute on Aging (Drs Cutler, Haxby, and Kay, Mr Renfrew, and Ms Moore), the Departments of Pharmacy (Drs Narang and Lesko) and Nursing (Ms Ninos), Clinical Center, the Clinical Neuropharmacology (Dr Costa) and Clinical Psychobiology (Dr Potter) Branches, National Institute of Mental Health, and the Laboratory of Clinical Studies, National Institute of Alcohol Abuse and Alcoholism (Dr Linnoila), National Institutes of Health, Bethesda, Md.

Footnotes
Accepted for publication Dec 8,1984.

Reprint requests to National Institute on Aging, National Institutes of Health, Bldg 10, Room 12 S-235, Bethesda, MD 20205 (Dr Cutler).

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