Messiha F S
Brain Res Bull. 1983 Aug;11(2):233-41. doi: 10.1016/0361-9230(83)90197-1.
In vivo and in vitro studies have been presented to suggest an interrelationship between drugs used in the management of, or known for their induction of extrapyramidal disorder and certain dehydrogenase enzymes involved in this metabolic pathway of the biogenic amines. This relationship is discussed to advance a tentative hypothesis explaining a possible underlying mechanism and to provide an explanation for the implication of alcohol consumption in worsening of extrapyramidal symptoms during certain pharmacotherapy. The major neutral metabolites of the biogenic amines acted as substrate to or induced rat liver alcohol dehydrogenase (L-ADH) and drugs used in the management of tardive dyskinesia similarly induced L-ADH. This induction of L-ADH could enhance the metabolic biotransformation of the neutral metabolites of the monoamines. Conversely, drugs known to evoke extrapyramidal dyskinesias inhibited rat liver aldehyde dehydrogenase (L-ALDH). This inhibition of ALDH may give rise to toxic condensation products between biogenic amine aldehydes and their precursors which may be implicated in certain dyskinesias. It is proposed that one of the mechanisms underlying the biogenic amine involvement in the pathogenesis of certain extrapyramidal diseases may include a critical balance between their reductive and oxidative routes of metabolism.
体内和体外研究表明，用于治疗锥体外系疾病或已知可诱发锥体外系疾病的药物与参与生物胺这一代谢途径的某些脱氢酶之间存在相互关系。本文讨论这种关系，以提出一个初步假设，解释可能的潜在机制，并为在某些药物治疗期间饮酒会使锥体外系症状恶化的现象提供一种解释。生物胺的主要中性代谢产物可作为大鼠肝脏乙醇脱氢酶（L-ADH）的底物或诱导该酶，用于治疗迟发性运动障碍的药物也同样可诱导L-ADH。L-ADH的这种诱导作用可增强单胺类中性代谢产物的代谢生物转化。相反，已知可引发锥体外系运动障碍的药物会抑制大鼠肝脏醛脱氢酶（L-ALDH）。对ALDH的这种抑制作用可能会导致生物胺醛与其前体之间产生有毒的缩合产物，这可能与某些运动障碍有关。有人提出，生物胺参与某些锥体外系疾病发病机制的潜在机制之一可能包括其代谢的还原途径和氧化途径之间的关键平衡。
