Pharmacology of antidepressants--characteristics of the ideal drug.
Pharmacology of antidepressants--characteristics of the ideal drug.
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抗抑郁药的药理学——理想药物的特征。
DOI：
10.1016/s0025-6196(12)61375-5
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发表时间：
1994
影响因子：
8.9
通讯作者：
Richelson,E
中科院分区：
文献类型：
--
作者：
Richelson,E
目的介绍抗抑郁药的临床及基本药理特性，从而确定理想抗抑郁药的药理学标准。设计回顾了新的第二代抗抑郁药的药理学特征，提出了与那些老化合物的关系。材料和方法获得抗抑郁药的突触作用（抑制突触体摄取和阻断神经递质受体）的临床药理学和体外数据，用于较老的抗抑郁药和最近上市和批准的药物。这组抗抑郁药包括自1988年以来批准上市的六种新抗抑郁药，以及另外两种在美国以外作为抗抑郁药上市，但在美国被批准用于治疗强迫症的药物。因此，本文讨论了18种抗抑郁药物。结果所有抗抑郁药在治疗抑郁症方面似乎都同样有效，而且似乎没有哪种药物比另一种药物起效更快。尽管如此，抗抑郁药物在药代动力学变量（消除半衰期）上存在很大差异；对其他药物代谢的影响（通过抑制细胞色素p450系统）；阻断去甲肾上腺素、血清素和多巴胺再摄取的能力；以及阻断组胺H1、毒蕈碱乙酰胆碱、α-肾上腺素能和多巴胺d2受体的亲和力。抗抑郁药的大多数副作用可以用它们阻断摄取和阻断神经递质受体的作用来解释。结论新二代抗抑郁药与三环类及旧二代抗抑郁药相比具有明显的药理优势。这些优势从它们的突触效应中可以清楚地看到，在突触效应中，大多数较新的第二代抗抑郁药实际上没有对神经递质受体的阻断作用。虽然较新的第二代抗抑郁药比旧的化合物更接近理想的抗抑郁药，但没有一种完全符合理想药物的标准。
ObjectiveTo describe the clinical and basic pharmacologic properties of antidepressants and thus define the pharmacologic criteria for the ideal antidepressant.DesignA review of the pharmacologic characteristics of the newer second-generation antidepressants is presented in relationship to those of the older compounds.Material and MethodsClinical pharmacologic and in vitro data on the synaptic effects of antidepressants (inhibition of synaptosomal uptake and blockade of neurotransmitter receptors) were obtained for the older antidepressants and for the more recently marketed and approved drugs. The group of antidepressants includes six new antidepressants approved for marketing since 1988 and two additional drugs marketed outside the United States as antidepressants but approved for use in the United States for obsessive-compulsive disorder. Thus, 18 antidepressant drugs are discussed.ResultsAll antidepressants seem to be equally efficacious in treating depression, and no drug seems to work more rapidly than another. Nonetheless, antidepressant drugs differ substantially in pharmacokinetic variables (elimination half-lives); in their effects on the metabolism of other drugs (by inhibiting the cytochrome P450system); in their potencies for blocking the reuptake of norepinephrine, serotonin, and dopamine; and in their affinities for blocking histamine H1, muscarinic acetylcholine, α-adrenergic, and dopamine D2receptors. Most side effects of antidepressants can be explained by their effects on blocking uptake and on blocking neurotransmitter receptors.ConclusionThe newer second-generation antidepressants have distinct pharmacologic advantages in comparison with the tricyclic antidepressants and the older second-generation compounds. These advantages are clearly seen from their synaptic effects, in which most newer second-generation antidepressants are practically devoid of blocking effects at neurotransmitter receptors. Although the newer second-generation antidepressants are much closer to being the ideal antidepressant than are the older compounds, none completely fulfills the criteria for being the ideal drug.