Effects of idebenone on monoamine metabolites in cerebrospinal fluid of patients with cerebrovascular dementia.
Monoamine metabolites and norepinephrine (NE) in the cerebrospinal fluid of patients with cerebrovascular dementia were measured to study the effects of administration of idebenone. Six patients with cerebral infarction and one with cerebral hemorrhage (mean age 65.4 years) were enrolled as subjects. All the patients had mental and intelligence impairment which was evaluated by the Hasegawa's Dementia Rating (DR) Scale. The patients were medicated with a 90 mg/day dose of idebenone for 1 to 2 months, and homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and NE in the cerebrospinal fluid were determined by high-performance liquid chromatography before and after the medication of idebenone. Before the medication, the level of HVA was 21.7 +/- 1.4 ng/ml (mean +/- SE), which was significantly lower (p less than 0.01) as compared with that in control subjects of similar age. The level of 5-HIAA was 18.5 +/- 2.7 ng/ml, and that of MHPG 9.5 +/- 0.7 ng/ml, both of which were lower than those of the controls, though statistically not significant. NE was similar to the control value. After administration of idebenone, HVA measured was 27.1 +/- 3.2 ng/ml, showing a tendency to increase. The levels of 5-HIAA and MHPG were 26.7 +/- 2.3 ng/ml and 10.7 +/- 0.6 ng/ml, respectively, which were significantly (p less than 0.05) higher than the premedication values. The percentages of the change were 12.8 +/- 8.0 for HVA, 58.2 +/- 18.5 for 5-HIAA and 14.2 +/- 5.0 for MHPG. The score of the DR scale was improved by 5 or less after the idebenone medication in most subjects. HVA and 5-HIAA increased markedly in the patients who showed a tendency of improvement of mental impairment as evaluated by the DR scale. The results suggested that idebenone would improve abnormalities in neurotransmitters of patients with cerebrovascular dementia, especially promoting serotonin turnover.
Kawakami
M
M
3rd Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Itoh
T
T
D000368:Aged; D000369:Aged, 80 and over; D016227:Benzoquinones; D015306:Biogenic Monoamines / Q000134:cerebrospinal fluid* / Q000378:metabolism; D015140:Dementia, Vascular / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000378:metabolism; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D011809:Quinones / Q000494:pharmacology*; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D015306:Biogenic Monoamines; D011809:Quinones; D014451:Ubiquinone; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; C036619:idebenone; D006719:Homovanillic Acid