5-[I- ]Iodo-3(2(S)-azetidinylmethoxy)pyridine, a radioiodinated analog of A-85380 for in vivo studies of central nicotinic acetylcholine receptors
Open accessAbstract
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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[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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BindingDB (2012) · UC San Diego · doi:10.7270/q21c1vf8
- 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
- hybrid
- doi.org
- Licence
- 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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