Cited by 58Nicotinic Acetylcholine Receptors StudyRadiopharmaceutical Chemistry and ApplicationsPharmacological Receptor Mechanisms and Effects

5-[I- ]Iodo-3(2(S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A-85380 for in vivo studies of central nicotinic acetylcholine receptors

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Musachio, John L., Scheffel, Ursula, Finley, Paige A., Zhan, Yougen, Mochizuki, Takao, Wagner, Henry N., Dannals, Robert F.·1998·Life Sciences

Abstract

The in vivo biodistribution profile of the novel nicotinic acetylcholine receptor (nAChR) radioligand 5-[I-125/123]Iodo-3(2(S)-azetidinylmethoxy)pyridine, [I-125/123]-5-IA, in mouse brain was examined. This radiotracer displayed good brain penetration (3.1% of the injected dose (ID) in whole brain at 15 min post-radioligand injection). Radioligand distribution was consistent with the density of high affinity nAChRs with highest uptake observed in the nAChR-rich thalamus (14.9 %ID/g at 60 min), moderate uptake in cortex (8.5 %ID/g at 60 min), and lowest uptake in the cerebellum (2.4 %ID/g at 60 min). Pretreatment with several different nAChR agonists (A-85380, (-)-nicotine, cytisine) significantly inhibited [I-125]-5-IA binding in all brain regions studied (P < 0.01) demonstrating the high specificity of the radioligand for nAChRs. Blocking doses of the muscarinic antagonist scopolamine and the non-competitive nAChR channel blocker mecamylamine had no significant effect on radioactive uptake supporting the in vitro selectivity of [I-125]-5-IA for the nAChR component of the cholinergic system. [I-125]-5-IA binding sites were shown to be saturable with unlabeled 5-IA. With a relatively low acute toxicity (LD50 > 3 mg/kg via intravenous injection in mice) and high in vivo specificity and selectivity, 5-IA labeled with the imaging radionuclide I-123 may prove useful for single photon emission computed tomography (SPECT) studies of nAChRs in human subjects.

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Crossref · 10.1016/s0024-3205(98)00180-5

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  • [123I]5-IA is a radioligand that has specificity for the agonist binding site on β2*-nAChRs.

    “With the recent development of [ 123 I]5-IA-85380 ([ 123 I]5-IA), a radioligand that has specificity for the agonist binding site on ␤ 2 *- nAChRs (Musachio et al., 1998(Musachio et al., , 1999;;Horti et al., 1999)”

    From Human Tobacco Smokers in Early Abstinence Have Higher Levels of β<sub>2</sub>* Nicotinic Acetylcholine Receptors than Nonsmokers (2006) · cites this paper as Musachio et al., 1998

    The Results (page not provided) show that nAChR agonists inhibited [125I]5-IA binding in mouse brain, and the Discussion reports specificity for central nAChRs. However, the Discussion only predicts selectivity for the α4β2 subtype; it does not establish specificity for the agonist binding site on β2*-nAChRs. (LLM, conf=0.85)

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Research works printed but not linked: 2

  1. W.A. CORRIGALL, K.B.J. FRANKLIN, K.M. COEN and P.B.S. Clarke, Psychopharmacol. 107 285-289 (1992). Vol. 62, No. 22,1998 In Ww Studies of Radioiodinatd A-S.5380 PI.27 3. 4. 2: 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
  2. M. KASSIOU, U.A. SCHEFFEL, H.T. RAVERT, W.B. MATHEWS, J.L. MUSACHIO, E.D. LO,NDON and R.F. DANNALS, Life Sci. (in press).

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Authors
Musachio, J. L., Scheffel, U., Finley, P. A., Zhan, Y., Mochizuki, T., Wagner, H. N., & Dannals, R. F.
Affiliations
Johns Hopkins University (US)
Corresponding author
Musachio, John L.
Venue
Life Sciences
Publisher
Elsevier BV
Published
1998-04
Volume
62
Issue
22
Pages
PL351-PL357
ISSN
0024-3205 (ISSN-L)
OpenAlex
W2086087139
Cited by
57
References
16
Citations by year
2022: 1 · 2018: 1 · 2012: 1
FWCI
2.48
Type
journal article
Language
en
Open access
Locations
  • Life Sciences (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
Keywords
nicotinic acetylcholine receptors, iodine-123, tissue distribution, thalamus, brain penetration, receptor selectivity, mecamylamine, scopolamine, SPECT imaging, cholinergic system
MeSH terms
Quinolizidine Alkaloids, Alkaloids, Animals, Azetidines, Azocines, Binding Sites, Brain, Dose-Response Relationship, Drug, Iodine Radioisotopes, Male, Mecamylamine, Nicotine, Quinolizines, Radionuclide Imaging, Receptors, Nicotinic, Scopolamine, Tissue Distribution, Muscarinic Antagonists, Nicotinic Antagonists, Mice

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