[125I]IPH, an epibatidine analog, binds with high affinity to neuronal nicotinic cholinergic receptors

J Pharmacol Exp Ther. 1997 Jul;282(1):445-51.

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 < 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoradiography
  • Binding Sites
  • Brain / metabolism*
  • Bridged Bicyclo Compounds, Heterocyclic / metabolism*
  • Male
  • Nicotinic Agonists / metabolism*
  • Pyridines / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Nicotinic / metabolism*
  • Stereoisomerism

Substances

  • 2-(2-iodo-5-pyridyl)-7-azabicyclo(2.2.1)heptane
  • Bridged Bicyclo Compounds, Heterocyclic
  • Nicotinic Agonists
  • Pyridines
  • Receptors, Nicotinic
  • epibatidine