脳血管障害の知的機能低下例における髄液中モノアミン代謝物質へのCV−2619（イデベノン）錠の影響

EFFECTS OF IDEBENONE ON MONOAMINE METABOLITES IN CEREBROSPINAL FLUID OF PATIENTS WITH CEREBROVASCULAR DEMENTIA

　抄録　脳血管性痴呆患者例の髄液について，homovanillic acid（HVA）, 5-hydroxyindole　aceticacid（5-HIAA），3-methoxy-4-hydroxyphenylethylenglycol（MHPG）， norepinephrine（NE）を高速液体クロマトグラフィーを用いて測定し，6-（10-hydroxydecyl）-2，3-dimethoxy-5-methyl-1， 4-benzoquinone（イデベノン，CV-2619）錠投与による影響を検討した。また，髄液mono-amine metabolitesの動向と精神機能との関連を検討した。脳血管性痴呆患者の髄液HVAは対照群に比べて有意に減少（P＜0.01）し，5-HIAA，MHPGは低値傾向を示した。NEは対照群と大差はなかった。CV-2619を90mg／日，1〜2カ月投与後，髄液HVAは増加傾向を示し，5-HIAA（P＜0.05），MHPG（P＜0．05）は有意に増加した。CV-2619投与後の投与前値からの変化率は5-HIAAにおいて最大であり，CV-2619投与による影響は5-HIAAで顕著であった。また，CV-2619投与後，長谷川式DRスヶ一ルが改善傾向を示した例で，　HVA，5-HIAAの増加は顕著であった。以上の結果より，CV-2619は脳血管性痴呆患者の神経伝達物質異常を改善し，特にserotoninのturnoverを促進することが示唆された。

Elucidation of the alterations of intracerebral neurotransmitters in cerebrovascular dementia is of prime importance not only in revealing patho-physiological mechanism but also in developing the therapy for the disease. We measured mono-amine metabolites and norepinephrine (NE) in cerebrospinal fluid of patients with cerebrovascular dementia, to study the effects of administration of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-metyl-1,4-benzoquinone (idebenone, CV-2619).

Six patients with cerebral infarction and 1 with cerebral hemorrhage, at the mean age of 65.4 years, were enrolled as subjects. All patients had mental and intelligent impairment, and the Hase-gawa's Dementia Rating (DR) Scale was performed. The patients were medicated with 90 mg daily dose of CV-2619 for 1 to 2 months, and homova-nillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG), NE in cerebrospinal fluid were deter-mined by high-performance liquid chromatography before and also after the medication. Before the medication, HVA was 21.7±1.4 ng/ml (mean±SE), which was significantly low (p<0.01), compared with controls at a similar age : 5-HIAA was 18.5 ±2.7 ng/ml, and MHPG, 9.5±0.7 ng/ml, both of which were not significantly low, but tended to be low, compared with the controls. NE was similar to the control value.

With the administration of CV-2619, HVA measured 27.1±3.2 ng/ml, showing a tendency to increase ; 5-HIAA was 26.7±2.3 ng/ml, andMHPG, 10.7±0.6 ng/ml, both of which increased significantly (p<0.05), compared with the respec-tive premedication values. The pre-postmedication change ratio (%) was 12.8±8.0 (mean±SE) for HVA, 58.2±18.5 for 5-HIAA, and 14.2±5.0 for MHPG : the CV-2619 medication thus exerted a prominent effect on 5-HIAA.

The DR scale improved by a score of 5 or less with the CV-2619 medication in most subjects, which was not sufficient to make a definite clinical interpretation, while HVA and 5-HIAA increased markedly in the patients showing a tendency for the DR scale to improve slightly.

These results suggested that CV-2619 would improve abnormalities in neurotransmitters of patients with cerebrovascular dementia, especially promoting serotonin turnover.