Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro.
Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro.
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发表时间：
1984-07
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通讯作者：
E. Richelson;A. Nelson
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作者：
E. Richelson;A. Nelson
使用放射性配体结合技术，我们确定了一系列抗抑郁药在尸检中获得的正常人脑组织的组胺H1、毒蕈碱乙酰胆碱、α-1和α-2肾上腺素能和多巴胺（D-2）受体上的平衡解离常数（KDS）。除了D-2受体外，总共研究了25种不同的抗抑郁药，D-2受体的数量为13种（包括抗抑郁药的代谢产物）。在研究的所有受体相互作用中，组胺H1受体通常是这类化合物的最有效相互作用，这与使用动物组织作为受体来源的研究结果一致。在人脑组胺H1受体，抗抑郁药仍然是已知的最有效的组胺H1拮抗剂，尽管它们对人类受体的亲和力低于动物受体。多塞平对受体作用最强和最弱（KD = 0.24 nM）和氟伏沙明（KD = 109 μ M）在组胺H1受体，阿米替林（KD = 18 nM）和曲唑酮（KD = 324 μ M）在毒蕈碱受体多塞平（KD = 24 nM）和维洛沙嗪（KD = 14 μ M）在α-1受体，米安色林（KD = 73 nM）和安非他酮（KD = 81 μ M）分别作用于α-2受体，阿莫西林（KD = 160 nM）和曲唑酮（KD = 3800 nM）分别作用于D-2受体。一般来说，与旧药物相比，新化合物对这些受体的亲和力往往较低。
Using radioligand binding techniques, we determined the equilibrium dissociation constants (KDS) for a series of antidepressants at the histamine H1, muscarinic acetylcholine, alpha-1 and alpha-2 adrenergic and dopamine (D-2) receptors of normal human brain tissue obtained at autopsy. Twenty-five different antidepressants were studied at all but the D-2 receptor at which the number was 13 (including a metabolite of an antidepressant). Of all the receptor interactions studied, that at the histamine H1 receptor was in general the most potent interaction of this class of compounds, corresponding to results from studies using animal tissue as the source of receptors. At the human brain histamine H1 receptor, antidepressants remained among the most potent histamine H1 antagonists known, although their affinities for human receptors were lower than those for animal receptors. The most potent and the least potent compounds at the receptors were doxepin (KD = 0.24 nM) and fluvoxamine (KD = 109 microM) at the histamine H1 receptor, amitriptyline (KD = 18 nM) and trazodone (KD = 324 microM) at the muscarinic receptor, doxepin (KD = 24 nM) and viloxazine (KD = 14 microM) at the alpha-1 receptor, mianserin (KD = 73 nM) and bupropion (KD = 81 microM) at the alpha-2 receptor and amoxapine (KD = 160 nM) and trazodone (KD = 3800 nM) at the D-2 receptor, respectively. In general, compared to older drugs, the newer compounds tended to have lower affinities for these receptors.