Dávila-García M I, Musachio J L, Perry D C, Xiao Y, Horti A, London E D, Dannals R F, Kellar K J
Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007, USA.
J Pharmacol Exp Ther. 1997 Jul;282(1):445-51.
An analog of epibatidine (EB) was synthesized with an iodine atom in the 2 position of the pyridyl ring. This analog, (+/-)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane (IPH), as well as its two stereoisomers, displayed high affinity for neuronal nicotinic receptors; therefore, radioiodinated IPH, [125I]IPH, was synthesized with specific radioactivities consistently > 1000 Ci/mmol, and its properties as a radioligand for neuronal nicotinic receptors were evaluated. The characteristics of [125I]IPH binding in tissue homogenates appeared to be virtually identical to those reported for [3H]epibatidine binding; but the high specific radioactivity of [125I]IPH greatly facilitated measurements of nicotinic receptors in tissues with relatively low receptor densities and/or where tissues are in limited supply. Autoradiography with [125I]IPH provided clear localization of nicotinic receptors in brain and adrenal gland after film exposure times of < or = 2 days. We conclude that [125I]IPH will be a very useful radioligand for the study of neuronal nicotinic receptors in brain and in peripheral ganglia.
在吡啶环的2位带有碘原子的埃博霉素（EB）类似物被合成出来。这种类似物，（±）-外型-2-（2-碘-5-吡啶基）-7-氮杂双环[2.2.1]庚烷（IPH），以及它的两种立体异构体，对神经元烟碱型受体显示出高亲和力；因此，具有始终大于1000居里/毫摩尔的比活度的放射性碘标记的IPH，即[¹²⁵I]IPH被合成出来，并对其作为神经元烟碱型受体放射性配体的性质进行了评估。[¹²⁵I]IPH在组织匀浆中的结合特性似乎与报道的[³H]埃博霉素结合特性几乎相同；但是[¹²⁵I]IPH的高比活度极大地促进了对受体密度相对较低和/或组织供应有限的组织中烟碱型受体的测量。用[¹²⁵I]IPH进行放射自显影，在胶片曝光时间≤2天之后，能清晰地定位脑和肾上腺中的烟碱型受体。我们得出结论，[¹²⁵I]IPH将是研究脑和外周神经节中神经元烟碱型受体的一种非常有用的放射性配体。
