Effects of acute lorazepam administration on aminergic activity in normal elderly subjects: relationship to performance effects and apolipoprotein genotype.
The effects of acute lorazepam challenges on plasma (p) HVA, MHPG, and 5-HIAA, and their relationship to drug-induced cognitive and motor deficits and the apolipoprotein (APOE)-epsilon4 allele were examined. Eighteen healthy elderly (8 epsilon4 carriers) received placebo or acute oral lorazepam doses (0.5 mg or 1 mg) in random sequence, 1-week apart. Cognitive assessment and plasma levels of pHVA, pMHPG, and p5-HIAA were determined at baseline and at 1, 2.5, and 5 h postchallenge. There was no drug-to-placebo difference in monoamine levels and no consistent relationship between changes in monoamine levels and cognitive performance, regardless of epsilon4 status. However, the 1.0 mg dose increased p5-HIAA in epsilon4 carriers, whereas it caused a reduction in noncarriers. Higher baseline pMHPG and p5-HIAA levels were associated with better baseline memory. The epsilon4 allele may modulate the effect of lorazepam on p5-HIAA, but further studies are needed to confirm this finding and elucidate its possible significance.
Pomara
Nunzio
N
Geriatric Psychiatry Program, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. Pomara@nki.rfmh.org
Willoughby
Lisa M
LM
Hashim
Audrey
A
Sershen
Henry
H
Sidtis
John J
JJ
Wesnes
Keith
K
Greenblatt
David J
DJ
Lajtha
Abel
A
D000368:Aged; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D053327:Apolipoprotein E4; D001053:Apolipoproteins / Q000235:genetics*; D001057:Apolipoproteins E / Q000187:drug effects / Q000235:genetics*; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics*; D005838:Genotype; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008140:Lorazepam / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D012044:Regression Analysis
D014151:Anti-Anxiety Agents; D053327:Apolipoprotein E4; D001053:Apolipoproteins; D001057:Apolipoproteins E; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D008140:Lorazepam; D006719:Homovanillic Acid