Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites.
Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites.
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发表时间：
1997-12
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通讯作者：
M. Owens;W. N. Morgan;S. Plott;C. Nemeroff
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作者：
M. Owens;W. N. Morgan;S. Plott;C. Nemeroff
在过去的几年中，已将几种抑制5-羟色胺（SERT）和去甲肾上腺素转运蛋白（NET）的新抗抑郁药引入了临床实践。该报告与其他抗抑郁药相比，该报告侧重于在血清素能和去甲肾上腺素能系统中的进一步的药理学表征及其代谢产物。通过使用放射性结合测定法，我们测量了大鼠和人类Sert和Net的13种抗抑郁药和6种代谢产物的亲和力（Ki）。还确定了八种抗抑郁药和三种代谢产物的Ki值，用于大鼠5-HT1A，5-HT2A和毒蕈碱胆碱能受体，豚鼠猪组胺1受体以及人α-1和α-2受体。这些数据可用于预测副作用谱和抗抑郁药的药效药物药物相互作用的潜力。特别令人感兴趣的是，普遍认为是选择性SERT拮抗剂的Paroxetine对网络具有适度的高亲和力，而Venlafaxine被描述为“双重摄取抑制剂”，对网络具有较弱的亲和力。我们观察到大鼠和人类转运蛋白之间的SERT（r = 0.965）或净（r = 0.983）亲和力的显着相关性。毒蕈碱胆碱能和净亲和力之间也观察到显着的相关性。 5-HT1A，5-HT2A，组胺1，alpha-1和alpha-2受体的亲和力之间存在几个显着的相关性。这些新发现的发现，并未广泛描述，表明这些实验中研究的许多单独药物具有某种结构特征，这些特征决定了对几种G蛋白偶联但不是毒桃体受体的亲和力。
Several new antidepressants that inhibit the serotonin (SERT) and norepinephrine transporters (NET) have been introduced into clinical practice the past several years. This report focuses on the further pharmacologic characterization of nefazodone and its metabolites within the serotonergic and noradrenergic systems, in comparison with other antidepressants. By use of radioligand binding assays, we measured the affinity (Ki) of 13 antidepressants and 6 metabolites for the rat and human SERT and NET. The Ki values for eight of the antidepressants and three metabolites were also determined for the rat 5-HT1A, 5-HT2A and muscarinic cholinergic receptors, the guinea pig histamine1 receptor and the human alpha-1 and alpha-2 receptors. These data are useful for predicting side effect profiles and the potential for pharmacodynamic drug-drug interactions of antidepressants. Of particular interest were the findings that paroxetine, generally thought of as a selective SERT antagonist, possesses moderately high affinity for the NET and that venlafaxine, which has been described as a "dual uptake inhibitor", possesses weak affinity for the NET. We observed significant correlations in SERT (r = 0.965) or NET (r = 0.983) affinity between rat and human transporters. Significant correlations were also observed between muscarinic cholinergic and NET affinity. There are several significant correlations between affinities for the 5-HT1A, 5-HT2A, histamine1, alpha-1 and alpha-2 receptors. These novel findings, not widely described previously, suggest that many of the individual drugs studied in these experiments possess some structural characteristic that determines affinity for several G protein-coupled, but not muscarinic, receptors.