Abstract

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 ≤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.