Rat brain binding sites for pramipexole, a clinically useful D3-preferring dopamine agonist
Rat brain binding sites for pramipexole, a clinically useful D3-preferring dopamine agonist
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普拉克索（一种临床上有用的 D3 偏好多巴胺激动剂）的大鼠脑结合位点
DOI：
10.1016/0304-3940(95)11857-s
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发表时间：
1995
影响因子：
2.5
通讯作者：
M. Piercey
中科院分区：
文献类型：
--
作者：
Marlene Catnacho;E. L. Walker;Dawna L. Evans;M. Piercey
普拉克索（PPX）目前正在评估用于治疗精神分裂症和帕金森病。在对多巴胺（DA[D2]受体亚家族的克隆亚型的研究中，与D2和D4亚型相比，PPX对D3具有更高的亲和力;与7-[3 H]羟基-N，N-二-正丙基-2-氨基四氢化萘（7-OH-DPAT[）不同，它不结合σ位点。使用[3 H]PPX（5 nM，62 Ci/mmol）的受体结合放射自显影评价大鼠脑内PPX结合位点的分布。与其对D3结合位点的偏好一致，在Calleja（ICj）的胰岛中发现了最高浓度的[3 H]PPX结合位点，先前报道含有D3但不含D2或D4 mRNA。[3 H]PPX结合在其他中脑边缘区也很高，如丘脑核（N. accum）、嗅结节和杏仁核。[3 H]PPX结合率也高尾状核（镉），虽然略低于中脑边缘区。在多巴胺能神经元胞体丰富的腹侧被盖区和黑质，[3 H]PPX结合位点较少。因此，虽然PPX最有力地刺激DA自身受体，PPX结合位点有其最高浓度的投射区含有DA末端和突触后受体。由于PPX对D3受体亚型的优先亲和力及其产生的高中脑边缘结合，它可能具有治疗精神病和/或神经系统疾病的独特治疗特征。
Pramipexole (PPX[ is currently being evaluated for treatment of schizophrenia and Parkinson's disease. In studies with cloned subtypes of the dopamine (DA[ D2receptor subfamily, PPX has higher affinity for the D3compared to the D2and D4subtypes; unlike 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT[, it does not bind to sigma sites. Receptor binding autoradiography with [3H]PPX (5 nM, 62 Ci/mmol) was used to evaluate the distribution of PPX binding sites within the rat brain. Consistent with its preference for D3-binding sites, the highest concentrations of [3H]PPX binding sites were found in the islets of Calleja (ICj), previously reported to contain D3but not D2or D4mRNA. [3H]PPX binding was also high in other mesolimbic areas such as the nucleus accumbens (N. accum), olfactory tubercle, and amygdala. [3H]PPX binding was also high in caudate (Cd), although slightly less than in mesolimbic areas. Less [3H]PPX binding sites were found in ventral tegmental area (VTA) and substantia nigra, areas rich in cell bodies for DA neurons. Thus, although PPX most potently stimulates DA autoreceptors, PPX binding sites have their highest concentrations in projection areas containing both DA terminal and postsynaptic receptors. Because of PPX's preferential affinity for the D3receptor subtype and its resultant high mesolimbic binding, it could have a unique therapeutic profile for treatment of psychiatric and/or neurological diseases.
纹状体多巴胺自身受体的受体储备：对多巴胺激动剂选择性的影响。
影响因子：
5
作者：
Meller,E;Helmer-Matyjek,E;Bohmaker,K;Adler,CH;Friedhoff,AJ;Goldstein,M
通讯作者：
Goldstein,M