CYP2D屬于細胞色素P450（CYP450）家族，是一類重要的藥物代謝酶。CYP2D介導(dǎo)約25%的臨床藥物代謝，包括抗抑郁藥、抗心律失常藥、鎮(zhèn)痛藥、抗腫瘤藥等；同時其活性也會被某些藥物，如氟西汀、普萘洛爾等抑制，進而導(dǎo)致與CYP2D底物藥物聯(lián)合使用時，藥物不良反應(yīng)的發(fā)生或加重。此外，CYP2D可介導(dǎo)腦內(nèi)部分內(nèi)源性神經(jīng)遞質(zhì)，如多巴胺和5-羥色胺合成的替代途徑和維持神經(jīng)類固醇，如四氫孕酮的腦內(nèi)穩(wěn)態(tài)。這提示CYP2D可能在中樞神經(jīng)系統(tǒng)的調(diào)節(jié)中發(fā)揮作用。研究表明，性激素以及過氧化物酶體增殖物激活受體（PPARs）、法尼類X受體（FXR）、肝細胞核因子4α（HNF4α）等核受體可以調(diào)控CYP2D mRNA水平和蛋白表達。多種生理和病理因素可能會改變CYP2D的表達和功能，進而影響其底物藥物的處置和藥效學(xué)。本文對CYP2D的結(jié)構(gòu)、功能、調(diào)控因素以及生理和疾病狀態(tài)下CYP2D表達和功能的改變、CYP2D抑制劑等研究進展進行綜述，為臨床更安全及合理用藥提供參考。

CYP2D, a member of the Cytochrome P450 family, is an important class of drug-metabolizing enzymes. CYP2D mediates about 25% of clinical drug metabolism, including antidepressants, antiarrhythmics, analgesics, antineoplastic drugs etc. At the same time, its activity is also inhibited by certain drugs, such as fluoxetine, propranolol, etc., which lead to the occurrence or aggravation of adverse drug reactions when combined with CYP2D substrate drugs. In addition, CYP2D mediates alternative pathways for the synthesis of some endogenous neurotransmitters in the brain, such as dopamine and serotonin, and maintains homeostasis of neurosteroids such as allopregnanolone in the brain. This suggests that CYP2D may play a role in the regulation of the central nervous system. Studies have shown that sex hormones and nuclear receptors including PPARs, FXR, and HNF4α can regulate mRNA and protein expressions of CYP2D. A variety of physiological and pathological factors may alter the expression and function of CYP2D, which in turn affects the disposal and pharmacodynamics of its substrate drugs. This review provides an overview of the structure, function, regulatory factor, as well as the changes of CYP2D expression and function in physiological and disease state.

R969.1

國家自然科學(xué)基金面上項目（82073922）