English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Synthesis and Characterization of Binding of 5-[76Br] Bromo-3-[[2(S)-Azetidinyl]methoxy]pyridine, a Novel Nicotinic Acetylcholine Receptor Ligand, in Rat Brain

Sihver, W., Fasth, K.-J., Horti, A., Koren, A., Bergström, M., Lu, L., et al. (1999). Synthesis and Characterization of Binding of 5-[76Br] Bromo-3-[[2(S)-Azetidinyl]methoxy]pyridine, a Novel Nicotinic Acetylcholine Receptor Ligand, in Rat Brain. Journal of Neurochemistry: official journal of the International Society for Neurochemistry, 73(3), 1264-1272. doi:10.1046/j.1471-4159.1999.0731264.x.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Sihver, W, Author
Fasth, K-J, Author
Horti, AG, Author
Koren, AO, Author
Bergström, M, Author
Lu, L, Author
Hagberg, G1, Author              
Lundqvist, H, Author
Dannals, RF, Author
London, ED, Author
Nordberg, A, Author
Långström, B, Author
Affiliations:
1External Organizations, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: 5-[76Br]Bromo-3-[[2(S)-azetidinyl]methoxy]-pyridine ([76Br]BAP), a novel nicotinic acetylcholine receptor ligand, was synthesized using [76Br]bromide in an oxidative bromodestannylation of the corresponding trimethylstannyl compound. The radiochemical yield was 25%, and the specific radioactivity was on the order of 1 Ci/μmol. The binding properties of [76Br]BAP were characterized in vitro and in vivo in rat brain, and positron emission tomography (PET) experiments were performed in two rhesus monkeys. In association experiments on membranes of the cortex and thalamus, >90% of maximal specific [76Br]BAP binding was obtained after 60 min. The dissociation half-life of [76Br]BAP was 51 ± 6 min in cortical membranes and 56 ± 3 min in thalamic membranes. Saturation experiments with [76Br]BAP revealed one population of binding sites with dissociation constant (KD) values of 36 ± 9 and 30 ± 9 pM in membranes of cortex and thalamus, respectively. The maximal binding site density (Bmax) values were 90 ± 17 and 207 ± 33 fmol/mg in membranes of cortex and thalamus, respectively. Scatchard plots were nonlinear, and the Hill coefficients were <1, suggesting the presence of a lower-affinity binding site. In vitro autoradiography studies showed that binding of [76Br]BAP was high in the thalamus and presubiculum, moderate in the cortex and striatum, and low in the cerebellum and hippocampus. A similar pattern of [76Br]BAP accumulation was observed by ex vivo autoradiography. In vivo, binding of [76Br]BAP in whole rat brain was blocked by preinjection of (S)(-)-nicotine (0.3 mg/kg) by 27, 52, 68, and 91% at survival times of 10, 25, 40, 120, and 300 min, respectively. In a preliminary PET study in rhesus monkeys, the highest [76Br]BAP uptake was found in the thalamus, and radioactivity was displaceable by ~60% with cytisine and by 50% with (S)(-)-nicotine. The data of this study indicate that [76Br]BAP is a promising radioligand for the characterization of nicotinic acetylcholine receptors in vivo.

Details

show
hide
Language(s):
 Dates: 1999-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Neurochemistry : official journal of the International Society for Neurochemistry
  Other : J. Neurochem.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York : Raven Press [etc.]
Pages: - Volume / Issue: 73 (3) Sequence Number: - Start / End Page: 1264 - 1272 Identifier: ISSN: 0022-3042
CoNE: https://pure.mpg.de/cone/journals/resource/954925416956