Koller W C, Rueda M G
Department of Neurology, University of Kansas Medical Center, Kansas City 66160-7314, USA.
Neurology. 1998 Jun;50(6 Suppl 6):S11-4; discussion S44-8. doi: 10.1212/wnl.50.6_suppl_6.s11.
As the substantia nigra degenerates in Parkinson's disease (PD), the nigrostriatal pathway is disrupted, reducing striatal dopamine and producing PD symptoms. Although dopamine does not readily cross the blood-brain barrier, its precursor, levodopa, does. Levodopa is absorbed in the small bowel and is rapidly catabolized by aromatic-L-amino-acid decarboxylase (AADC) and catechol-O-methyltransferase (COMT). Because gastric AADC and COMT degrade levodopa, the drug is given with inhibitors of AADC (carbidopa or benserazide), and inhibitors of COMT will also enter clinical use. Although the exact site of decarboxylation of exogenous levodopa to dopamine in the brain is unknown, most striatal AADC is located in nigrostriatal dopaminergic nerve terminals. Newly synthesized dopamine is stored in the terminals and then released, stimulating postsynaptic dopamine receptors and mediating the antiparkinsonian action of levodopa. Dopamine agonists act directly on postsynaptic dopamine receptors, thus obviating the need for metabolic conversion, storage, and release. How the actions of dopaminergic drugs produce side effects and how these side effects should be managed are discussed.
在帕金森病（PD）中，随着黑质退化，黑质纹状体通路被破坏，纹状体多巴胺减少并产生PD症状。虽然多巴胺不易穿过血脑屏障，但其前体左旋多巴可以。左旋多巴在小肠被吸收，并迅速被芳香族L-氨基酸脱羧酶（AADC）和儿茶酚-O-甲基转移酶（COMT）分解代谢。由于胃中的AADC和COMT会降解左旋多巴，所以该药物与AADC抑制剂（卡比多巴或苄丝肼）一起给药，并且COMT抑制剂也将进入临床应用。虽然外源性左旋多巴在脑中脱羧转化为多巴胺的确切部位尚不清楚，但大多数纹状体AADC位于黑质纹状体多巴胺能神经末梢。新合成的多巴胺储存在神经末梢，然后释放，刺激突触后多巴胺受体并介导左旋多巴的抗帕金森作用。多巴胺激动剂直接作用于突触后多巴胺受体，因此无需进行代谢转化、储存和释放。文中讨论了多巴胺能药物的作用如何产生副作用以及应如何处理这些副作用。
