Vol. 282, Issue 1, 445-451, 1997

[¹²⁵I]IPH, an Epibatidine Analog, Binds with High Affinity to Neuronal Nicotinic Cholinergic Receptors¹

Martha I. Dávila-García, John L. Musachio, David C. Perry, Yingxian Xiao, Andrew Horti, Edythe D. London, Robert F. Dannals and Kenneth J. Kellar

Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20007 (M.I.D.-G., Y.X., K.J.K.); Department of Radiology, The Johns Hopkins University Medical Institutions, Baltimore, MD 21287 (J.L.M., R.F.D.); Department of Pharmacology, George Washington University School of Medicine, Washington, DC 20037 (D.C.P.); Brain Imaging Center, National Institute on Drug Abuse, Baltimore, MD 21224 (A.H., E.D.L.)

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.