Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer's disease

Psychopharmacology (Berl). 1987;91(3):293-6. doi: 10.1007/BF00518180.

Abstract

Deprenyl, a monoamine oxidase (MAO) inhibitor with selective effects on MAO type-B at low doses, was administered to 13 patients with dementia of the Alzheimer type (DAT), a disorder reported to be associated with increased brain MAO-B activity. Cerebrospinal fluid was obtained for measurement of three monoamine metabolites, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), by high pressure liquid chromatography with electrochemical detection. Deprenyl treatment (10 mg/day) for 3-4 weeks was associated with small but statistically significant reductions in HVA (21%) and 5-HIAA (15%) compared to baseline values. Subsequent administration of deprenyl at the higher dose of 40 mg/day for 3-4 more weeks led to greater reductions in HVA (40%) and MHPG (43%) than 5-HIAA (20%). These dose-dependent reductions are consistent with in vitro biochemical and anatomical data from primate brain suggesting that at low doses of deprenyl, MAO-B inhibition might be expected to selectively affect dopamine and serotonin-containing neurons, while at higher doses (which lead to MAO-A as well as MAO-B inhibition), noradrenergic neurons may become relatively more affected by the drug.

MeSH terms

  • Aging
  • Alzheimer Disease / cerebrospinal fluid*
  • Biogenic Amines / cerebrospinal fluid*
  • Dose-Response Relationship, Drug
  • Homovanillic Acid / cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Methoxyhydroxyphenylglycol / cerebrospinal fluid
  • Middle Aged
  • Phenethylamines / pharmacology*
  • Selegiline / pharmacology*

Substances

  • Biogenic Amines
  • Phenethylamines
  • Selegiline
  • Methoxyhydroxyphenylglycol
  • Hydroxyindoleacetic Acid
  • Homovanillic Acid