Evaluation of zimeldine in Alzheimer's disease. Cognitive and biochemical measures.
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.
Cutler
N R
NR
Haxby
J
J
Kay
A D
AD
Narang
P K
PK
Lesko
L J
LJ
Costa
J L
JL
Ninos
M
M
Linnoila
M
M
Potter
W Z
WZ
Renfrew
J W
JW
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D001792:Blood Platelets / Q000378:metabolism; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008568:Memory / Q000187:drug effects; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D010919:Placebos; D011581:Psychological Tests; D011930:Reaction Time / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D015031:Zimeldine / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
D010919:Placebos; D012701:Serotonin; D015031:Zimeldine; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D006719:Homovanillic Acid