L-threo-DOPSのマウス電撃痙攣に対する抑制効果

INHIBITORY EFFECTS OF L-TREAD-DOPS ON ELECTROSHOCK SEIZURE IN MICE

　抄録　l-norepinephrine （NE）の合成前駆物質であるL-threo−3,4-dihydroxyphenylserine。L-DOPS）の痙攣発作に及ぼす影響を，マウスの電撃痙攣モデルを用いて検討した。薬物は全て腹腔内に投与した。L-DOPS （200,400mg／kg）は最小電撃痙攣閾値に有意な影響を与えなかった。100から400mg／kgの量でL-DOPSは最大電撃痙攣（MES）を有意に阻止できなかったが，E／F比を用量依存的に減少させた。単独投与では抗痙攣効果のないnialamide （30mg／kg），　desipramine （20mg／kg）およびmaprotiline）（40mg／kg）と併用した場合，L-DOPSは有意にMESを阻止した。その際のED50（95％信頼限界）はそれぞれ210（145-305），160（100-256）および95（50-181） mg／kgであった。L-DOPSの抗痙攣作用は痙攣閾値の上昇によるものではなく，痙攣波の波及を抑制することによると考えられた。L-DOPSは痙攣の抑制機構におけるNEの役割の研究の上で，また臨床的には全般性強直間代痙攣に対する補助的薬物として有用であることが示唆された．

Effects of L-threo-3, 4-dihydroxyphenylserine (L-DOPS), a synthetic norepinephrine (NE) precursor, on electroshock seizure were studied in mice. All substances were administered intraperitoneally. Minimal electroshock seizure threshold (EST) was not significantly altered by L-DOPS at a dose of 200 or 400 mg/kg. L-DOPS was unable to abolish tonic extensions of hind legs in maximal electro-shock seizure (MES) test at doses from 100 to 400 mg/kg. However, it significanity reduced exten-sion/flexion (E/F) ratio in a dose-dependent manner. Futhermore, L-DOPS dose-dependently blocked maximal electroconvulsions in a combined use with nialamide (30 mg/kg), desipramine (20 mg/kg) or maprotiline (40 mg/kg) at so small doses as not to show any anticonvulsant effect when they were used alone. ED₅₀ (with 95% confidence limit) of L-DOPS in the combination treatments were 210 (145-305), 160 (100-256) and 95 (50-181) mg/kg respectively. Those results indicate that L-DOPS has an anticonvulsant property, which is potenti-ated by a MAO inhibitor or NE uptake blockers. It was presumed that the effect of L-DOPS was caused by the inhibition of spreading of seizure discharges. It was suggested that L-DOPS would be a useful substance for the investigation on a role of NE in experimental epilepsy and could be used clinically as an adjunct drug for generalized tonic-clonic convulsions.