INTERACTION OF NON-STEROIDAL ANTIESTROGENS WITH DOPAMINE RECEPTOR-BINDING
INTERACTION OF NON-STEROIDAL ANTIESTROGENS WITH DOPAMINE RECEPTOR-BINDING
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DOI：
10.1016/0022-4731(84)90028-1
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发表时间：
1984-01-01
影响因子：
4.1
通讯作者：
GHRAF, R
中科院分区：
文献类型：
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作者：
HIEMKE, C;GHRAF, R
测试了雌激素拮抗剂和激动剂与[3 H]螺哌利多、[3 H]多潘立酮、[3 H]二氢阿普洛尔、[3 H]二氢麦角隐亭、[3 H]多巴胺或[3 H]5-羟色胺竞争结合大鼠脑组织膜制备物的能力。发现具有胺侧链的非甾体三苯乙烯型抗雌激素恩氯米芬、硝米芬、他莫昔芬和祖氯米芬是[3 H]螺哌啶（Kd = 0.12 nM; Bmax [最大结合容量] = 101 fmol mg蛋白）和[3 H]多潘立酮（Kd = 0.62 nM; Bmax = 86 fmol mg蛋白）与纹状体膜结合的竞争性抑制剂。Ki值范围为4-12 μ M。Estradiol-17.beta. (Ki= 480 μ M）或己烯雌酚（Ki = 63 μ M）是低得多的有效抑制剂，表现出与[3 H]螺哌啶的体外结合的非竞争性相互作用。与多巴胺受体结合的抗雌激素相互作用的药理学相关性进行了讨论，在体内给药的化合物，如恶心和呕吐的不良反应。
The ability of estrogen antagonists and agonists to compete with [3H]spiroperidol, [3H]domperidone, [3H]dihydroalprenolol, [3H]dihydroergocryptine, [3H]dopamine or [3H]5-hydroxytryptamine for binding to membrane preparations from rat brain tissue was tested. The non-steroidal triphenylethylene-type antiestrogens with an amine side chain enclomiphene, nitromifene, tamoxifen and zuclomiphen were found to be competitive inhibitors of [3H]spiroperidol (Kd = 0.12 nM; Bmax [maximal binding capacity] = 101 fmol mg protein) and [3H]domperidone (Kd = 0.62 nM; Bmax = 86 fmol mg protein) binding to striatal membranes. The Ki values ranged from 4-12 .mu.M. Estradiol-17.beta. (Ki = 480 .mu.M) or diethylstilbestrol (Ki = 63 .mu.M) were much less effective inhibitors exhibiting noncompetitive interaction with the in vitro binding of [3H]spiroperidol. The pharmacological relevance of the antiestrogen interactions with dopamine receptor binding is discussed with respect to adverse effects of the in vivo administered compounds such as nausea and vomiting.