The metabolism of iodine-123 labelled 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine (NNC 13–8241) measured in human plasma is only minor
✍ Scribed by Kari K. Åkerman; Kim A. Bergström; Christer Halldin; Simo Lötjönen; Meixiang Yu; Tuomo Nikula; Jukka Hiltunen; Christian Foged; Jyrki T. Kuikka; Jari Tiihonen
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 130 KB
- Volume
- 13
- Category
- Article
- ISSN
- 0885-6222
No coin nor oath required. For personal study only.
✦ Synopsis
The imidazobenzodiazepine derivate 123 I-labelled 3-(5-cyclopropyl-1,2,4-oxadiazo-3-yl)-7-iodo-5,6-dihydro-5methyl-6-oxo-4H-imidazo [1,5-a][1,4]-benzodiazepine (NNC 13±8241) is a partial benzodiazepine agonist and binds with a high anity to the benzodiazepine receptor. The favourable kinetic properties indicate that [ 123 I]NNC 13±8241 is a promising SPET ligand. In the present study, an extensive examination of the metabolite pattern of [ 123 I]NNC 13±8241 in plasma and urine from seven healthy subjects was performed using gradient HPLC. After injection of [ 123 I]NNC 13±8241 into human beings, only one radioactive metabolite was found in plasma 3±300 min post injection. This polar metabolite eluted together with the solvent front fraction. The proportion of unchanged [ 123 I]NNC 13±8241 was 82±86 per cent during the entire study. In addition, two other radioactive metabolites were found in urine. The ®rst metabolite was lipophilic and eluted slightly before the parent compound [ 123 I]NNC 13±8241. The second metabolite eluted slightly after solvent front peak. The amount of unchanged [ 123 I]NNC 13±8241 in human urine was 9 per cent and the solvent front fraction contained 72 per cent of total radioactivity. No detectable radioactivity appeared with the same retention time as synthetisized nor-NNC 13±8241 in plasma or urine, which excludes the possibility of in vivo demethylation of [ 123 I]NNC 13±8241. In conclusion, the [ 123 I]NNC 13±8241 was found to have only a minor metabolism, which favours its use as a SPET tracer for quantitation of the benzodiazepine receptor.