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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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

Martha I. Dávila-García, John L. Musachio, David C. Perry, Yingxian Xiao, Andrew Horti, Edythe D. London, Robert F. Dannals and Kenneth J. Kellar
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 445-451;
Martha I. Dávila-García
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John L. Musachio
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David C. Perry
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Yingxian Xiao
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Andrew Horti
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Edythe D. London
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Robert F. Dannals
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Kenneth J. Kellar
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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

  • Send reprint requests to: Kenneth J. Kellar, Ph.D., Department of Pharmacology, Georgetown University School of Medicine, Washington DC 20007.

  • ↵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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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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

Martha I. Dávila-García, John L. Musachio, David C. Perry, Yingxian Xiao, Andrew Horti, Edythe D. London, Robert F. Dannals and Kenneth J. Kellar
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 445-451;

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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

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

Martha I. Dávila-García, John L. Musachio, David C. Perry, Yingxian Xiao, Andrew Horti, Edythe D. London, Robert F. Dannals and Kenneth J. Kellar
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 445-451;
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