Himori N, Mishima K
Department of Pharmacology, Nippon Roche Research Center, Kamakura, Japan.
Experientia. 1994 Oct 15;50(10):939-42. doi: 10.1007/BF01923483.
Orally administered Madopar (levodopa/benserazide 4:1) dose-dependently antagonized haloperidol-induced (1 mg/kg s.c.) catalepsy in MPP(+)-lesioned mice. Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy. The ability of tolcapone to increase the Madopar effect was significantly attenuated by high doses of 3-O-methyldopa (3-OMD) (800 mg/kg i.p.). This might suggest a competitive blockade of the active transport of levodopa through the blood-brain barrier. In conclusion, the inhibitory effect of tolcapone on the O-methylation of levodopa to 3-OMD by COMT is largely due to improved levodopa and dopamine availability in the brain, and to the reduced formation of 3-OMD.
口服美多芭（左旋多巴/苄丝肼 4:1）对 1-甲基-4-苯基吡啶离子（MPP⁺）损伤小鼠中氟哌啶醇（1 mg/kg，皮下注射）诱导的僵住症有剂量依赖性拮抗作用。用新型选择性儿茶酚-O-甲基转移酶（COMT）抑制剂托卡朋（30 mg/kg，口服）预处理，可轻微增强美多芭（15 mg/kg，口服）对氟哌啶醇诱导僵住症的拮抗作用。高剂量的 3-O-甲基多巴（3-OMD）（800 mg/kg，腹腔注射）可显著减弱托卡朋增强美多芭作用的能力。这可能提示其对左旋多巴通过血脑屏障的主动转运存在竞争性阻断。总之，托卡朋通过 COMT 抑制左旋多巴向 3-OMD 的 O-甲基化作用，很大程度上是由于提高了脑内左旋多巴和多巴胺的可用性，以及减少了 3-OMD 的形成。
