Brannan T, Prikhojan A, Yahr M D
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Brain Res. 1996 Apr 29;718(1-2):165-8. doi: 10.1016/0006-8993(96)00116-3.
The D stereoisomer of dihydroxyphenylalanine (D-DOPA) and its alpha-keto acid metabolite 3,4-dihydroxyphenylpyruvic acid (DHPPA) when infused into the striatum, significantly increased in vivo extracellular dopamine levels. Following D-DOPA administration, the cumulative increase in dopamine levels was 30% of the increase following L-DOPA: following DHPPA it was 11% that of L-DOPA. Rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra demonstrated brisk contralateral turning following each compound. The turning, however, was delayed by 10-20 min and total turning was 40% less following D-DOPA and 57% less following DHPPA than it was following L-DOPA. These data indicate that exogenously administered D-DOPA can be metabolized in vivo within the brain to dopamine and suggest this may occur via a transamination pathway in which DHPPA is an intermediary metabolite. The possible relevance of these findings to the treatment of Parkinson's disease is discussed.
将二羟基苯丙氨酸（D - DOPA）的D型立体异构体及其α - 酮酸代谢产物3,4 - 二羟基苯丙酮酸（DHPPA）注入纹状体后，可显著提高体内细胞外多巴胺水平。给予D - DOPA后，多巴胺水平的累积增加量为给予左旋多巴（L - DOPA）后增加量的30%；给予DHPPA后，该增加量为L - DOPA的11%。单侧6 - 羟基多巴胺诱导黑质损伤的大鼠在给予每种化合物后均出现明显的对侧旋转。然而，与给予L - DOPA相比，给予D - DOPA后的旋转延迟了10 - 20分钟，总旋转次数减少了40%，给予DHPPA后的旋转延迟了10 - 20分钟，总旋转次数减少了57%。这些数据表明，外源性给予的D - DOPA可在脑内于体内代谢为多巴胺，并提示这可能通过转氨途径发生，其中DHPPA是中间代谢产物。本文讨论了这些发现与帕金森病治疗的可能相关性。
