潜在多巴胺D4受体选择性放射性配体的神经药理学评估。
Neuropharmacological assessment of potential dopamine D4 receptor-selective radioligands.
作者信息
Kula N S, Tarazi F I, Baldessarini R J, Xu L, Bakthavachalam V, Pounds S, True C D
机构信息
Mailman Research Center, McLean Division of Massachusetts General Hospital, Belmont 02478, USA.
出版信息
Eur J Pharmacol. 1999 Feb 12;367(1):139-42. doi: 10.1016/s0014-2999(98)00980-7.
Radiolabeled dopamine D4 receptor-selective agents ([3H]1-benzyl-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine maleate; [3 H]PNU-101958. and [125I]1-[4-iodobenzyl]-4-[ N-(3-isopropoxy-2-pyridinyl)-N-methyl]-aminopiperidine; [125I]RBI-257) were prepared and characterized. With D4.2- and D2L receptor-transfected cell membranes, [3H]PNU-101958 showed high dopamine D4 receptor affinity and selectivity, and potent inhibition by dopamine D4 receptor-selective compounds. However, its binding with rat brain homogenates showed little regional selectivity, and pharmacology inconsistent with selective dopamine D4 receptor labeling. Autoradiography indicated partial displacement of [3H]PNU-101958 by unlabeled dopamine D4 receptor ligands without regional selectivity, and lack of selective labeling with [125I]RBI-257. The results encourage further efforts to develop better dopamine D4 receptor-selective radioligands.
制备并表征了放射性标记的多巴胺D4受体选择性试剂（[3H]1-苄基-4-[N-(3-异丙氧基-2-吡啶基)-N-甲基]-氨基哌啶马来酸盐；[3H]PNU-101958，以及[125I]1-[4-碘苄基]-4-[N-(3-异丙氧基-2-吡啶基)-N-甲基]-氨基哌啶；[125I]RBI-257）。在转染了D4.2和D2L受体的细胞膜上，[3H]PNU-101958表现出高多巴胺D4受体亲和力和选择性，并受到多巴胺D4受体选择性化合物的有效抑制。然而，它与大鼠脑匀浆的结合几乎没有区域选择性，且药理学特性与选择性多巴胺D4受体标记不一致。放射自显影显示未标记的多巴胺D4受体配体对[3H]PNU-101958有部分取代作用，但无区域选择性，并且[125I]RBI-257缺乏选择性标记。这些结果促使人们进一步努力开发更好的多巴胺D4受体选择性放射性配体。
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