Synthesis of a potential M1 muscarinic agent [76Br] bromocaramiphen

Article abstract of DOI:10.1002/(SICI)1099-1344(199605)38:5<471::AID-JLCR854>3.0.CO;2-Q

[⁷⁶Br]bromocaramiphen was prepared from the iodo-analogue by a Cu⁺ nucleophilic bromodeiodination exchange. The radiolabelling yield was 40-45%. The radiochemical and chemical purities assessed by radio-TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1-phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyclopemane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the pons tissues indicated that there was still 92% of unchanged radiotracer 30 mm p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pons, the cortex, the striatum and the cerebellum. These data suggest that [⁷⁶Br]bromocaramiphen is not a potential probe for investigating the status of central M₁ muscarinic receptors because of its high lipophilicity (log P_{7 4} = 2.4) and its affinity for sigma sites.