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[C‐11]N‐methylhomoepibatidine: radiolabelling and biodistribution studies in mice
Author(s) -
Patt J. T.,
Spang J. E.,
Westera G.,
Schubiger P. A.
Publication year - 2000
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(200002)43:2<127::aid-jlcr299>3.0.co;2-u
Subject(s) - chemistry , biodistribution , epibatidine , specific activity , partition coefficient , radiochemistry , yield (engineering) , stereochemistry , in vitro , chromatography , receptor , biochemistry , enzyme , materials science , nicotinic agonist , nicotinic acetylcholine receptor , metallurgy
The radiochemical synthesis of [C‐11]N‐methylhomoepibatidine ( 2 ) was accomplished by reacting homoepibatidine ( 1 ) and [C‐11]iodomethane. The radiochemical yield was in the range of 5 to 10% related to [C‐11]iodomethane. A high specific activity of 150 to 370 GBq/μmol at the end of synthesis was achieved. The partition coefficient was log P 7·4 =0·34. Biological evaluation was performed with the racemate in mice. High brain uptake was found. Compared to [C‐11]N‐methylepibatidine ( 4 ) data, which were achieved by the same experimental setup, the values of [C‐11]N‐methylhomoepibatidine ( 2 ) uptake in the brain were slightly lower (approximately 15%/g compared to 20%/g for [C‐11]N‐methylepibatidine ( 4 )). But in contrast to the homologous [C‐11]N‐methylepibatidine ( 4 ) the brain uptake curve decreased after approximately 15 minutes showing reversible binding to the receptor. Pretreatment of mice with (−)‐epibatidine ( 3 ) resulted in a considerably lower brain uptake while uptake in other tissues remained unchanged. Copyright © 2000 John Wiley & Sons, Ltd.