Parkinsonismに対するL-DOPA療法—臨床効果・副作用・尿中Catecholamine代謝物を中心に

TREATMENT OF PARKINSONISM WITH L-DOPA:MAINLY ON CLINICAL EFFECTS, SIDE EFFECTS AND URINARY METABOLITES OF CATECHOLAMINE

まえがき

　Parkinsonismの治療には従来anticholinergic agentsを主体として，これに補助的に精神安定剤，賦活剤，脳代謝促進剤などが用いられてきた。しかし脳内amine代謝の研究が進むに従い本症の主病変部位である線状体を主とする錐体外路系のdihydroxyphenylalanine （DOPA）—dopamine代謝が注目され，本症で該部のDOPA, dopa—mine，合成酵素DOPA decarboxylase，分解酵索mono—amine oxjdase （MAO），　catechol—0—methyltransferase，代謝物homovanillic acid （HVA）などの著明な低下〜消失が証明されるに及び，本症の治療に先駆物質であるDOPAを投与する試みがBarbeau^1）（1961）以来多くの欧米学者によりなされ，その卓効が認められるに至つた〈Birkmayer^3）（1962），　Cotzias^7）（1967），　Yahr^26）（1968），　Duvoisin^9）（1969），　Godwin-Austen^12）（1969），　Barbeau^2）（1969），　Mawdsley^17）（1970），　Peaston^22）（1970），　McDowell^18）（1970）〉。

　すなわち諸家の研究によるとDO PAはParkinsonismの主症状のうち主として無動〜寡動および筋強剛に有効であり，化学構造としてはL型DOPAが最も有効でD型は無効であること，脳内ではDOPAの型で血液脳関門を通過しdopamineに変化して作用すると考えられること，副作用としては悪心，嘔吐，食思不振，低血圧，特殊な不随意運動が多いこと，またL-DOPAにanti—cholinergic agentsやanti-MAO剤その他外科的療法の併用が一層有効であることなどが認められた。

Twenty eight patients with Parkinsonism were treated with L-DOPA. The administration method,clinical effects, side effects and urinary metabolites of catecholamine were studied in these patients, and the following results were obtained.

1. The effect of L-DOPA was proved in 25 cases with rigidity out of 28 (89. 3%), in 25 cases with akinesia or bradykinesia out of 28 (89. 3%) and in 14 cases with tremor out of 26 (53. 8%). In other symptoms such as expressions, speech, posture, gait and ADL (activity of daily living), considerable effects were obtained.

2. L-DOPA was administered increasingly from a low dose to the maintenance dose of 3-4 g per day. Nevertheless, some cases got considerably better at doses less than 3 g.

3. The combination use with usual anticholiner-gic agents increased the effect of L-DOPA.

4. The most frequent side effects were nausea, vomiting and anorexia, while hypotension, invol-untary movements, hallucination, sweating and palpitation were recorded in a few cases. All these adverse effects diminished or disappeared by carry-ing out symptomatic treatment or reducing the dose of L-DOPA.

5. The urine levels of DOPA, dopamine and homovanillic acid after administration of L-DOPA were somewhat varied according to the cases, where-as increase of vanillylmandelic acid was not observed.