(+)-[C-11]-cis-N-benzyl-normetazocine: a selective ligand for sigma receptors in vivo.
(+)-[C-11]-cis-N-benzyl-normetazocine: a selective ligand for sigma receptors in vivo.
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DOI：
10.1016/0024-3205(94)90051-5
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发表时间：
1994
期刊：
影响因子：
6.1
通讯作者：
J. Musachio;U. Scheffel;M. Stathis;H. Ravert;W. B. Mathews;R. Dannals
中科院分区：
文献类型：
--
作者：
J. Musachio;U. Scheffel;M. Stathis;H. Ravert;W. B. Mathews;R. Dannals
本文研究了新的σ受体配体（+）-[C-11]-cis-N-苄基-去甲甲甲唑辛（[C-11]-（+）-NBnNM）在小鼠脑内的体内生物分布。该放射性配体显示出高脑摄取和与σ受体密度一致的分布。脑放射性水平在注射后15分钟达到峰值，并在很大程度上维持（约100 mg/kg）。最大值的80%）。用几种不同的σ配体（氟哌啶醇、（+）-喷他佐辛、DuP 734、艾芬地尔）预处理在所有脑区中以剂量依赖性方式有效地抑制[C-11]-（+）-NBnNM结合。[C-11]-（+）-NBnNM结合位点被未标记的（+）-NBnNM饱和（ED 50 = 0.02 mg/kg），并被喷他佐辛的光学异构体对映选择性抑制。阻断剂量的多巴胺D2拮抗剂螺哌隆（1 mg/kg）未显著抑制[C-11]-（+）-NBnNM结合。用苯环利定（PCP）阻断剂1-[1-（2-噻吩基）环己基]哌啶（TCP）预处理未显著改变总脑组织放射性。因此，[C-11]-（+）-NBnNM与σ受体在体内具有高度的特异性和选择性结合，为在活体人脑中研究σ受体提供了极好的潜力。
Thein vivobiodistribution profile of the novel sigma (σ) receptor ligand (+)-[C-11]-cis-N-benzyl-normetazocine ([C-11]-(+)-NBnNM) in mouse brain was examined. This radioligand displayed high brain uptake and a distribution consistent with the density of σ receptors. Brain radioactivity levels peaked at 15 min postinjection and were largely maintained (ca. 80% of maximal values) up to 90 min postinjection. Pretreatment with several different σ ligands (haloperidol, (+)-pentazocine, DuP 734, ifenprodil) effectively inhibited [C-11]-(+)-NBnNM binding in a dose-dependent manner in all brain regions. [C-11]-(+)-NBnNM binding sites were shown to be saturable with unlabeled (+)-NBnNM (ED50 = 0.02 mg/kg) and enantioselectively inhibited by the optical isomers of pentazocine. A blocking dose of the dopamine D2 antagonist spiperone (1 mg/kg) did not significantly inhibit [C-11]-(+)-NBnNM binding. Pretreatment with the phencyclidine (PCP) blocker 1-[1-(2-thienyl)cyclohexyl] piperidine (TCP) did not significantly alter total brain tissue radioactivity. Thus, [C-11]-(+)-NBnNM binds with high specificity and selectivity to σ receptorsin vivoand offers excellent potential to study σ receptors in living human brainviapositron emission tomography.