Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease.
A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.
Heinonen
E H
EH
Orion Corporation Farmos, R&D Pharmaceuticals, Turku, Finland.
Savijärvi
M
M
Kotila
M
M
Hajba
A
A
Scheinin
M
M
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000523:psychology; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000134:cerebrospinal fluid*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D012642:Selegiline / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D014364:Tryptophan / Q000134:cerebrospinal fluid
D015306:Biogenic Monoamines; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D014364:Tryptophan; D009638:Norepinephrine