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.
Footnotes
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Send reprint requests to: Kenneth J. Kellar, Ph.D., Department of Pharmacology, Georgetown University School of Medicine, Washington DC 20007.
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↵1 This work was supported in part by National Institutes of Health Grant DA06486. The Brain Resource Center at Johns Hopkins University is supported by National Institutes of Health Grant AG05146.
- Abbreviations:
- ACh
- acetylcholine
- DHβE
- dihydro-β-erythroidine
- EB
- epibatidine
- IPH
- (±)-exo-2-(2-iodo-5-pyridyl)-7-azabicyclo[2.2.1]heptane
- HPLC
- high performance liquid chromatography
- Received January 8, 1997.
- Accepted March 10, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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[125I]IPH, an Epibatidine Analog, Binds with High Affinity to Neuronal Nicotinic Cholinergic Receptors
