SYNTHESIS OF A POTENTIAL M(1) MUSCARINIC AGENT [BR-76]BROMOCARAMIPHEN

[Br-76]bromocaramiphen was prepared from the iodo-analogue by a Cu+ nu cleophilic bromodeiodination exchange. The radiolabelling yield was 40 -45%. The radiochemical and chemical purities assessed by radio-TLC an d HPLC were 98%. The precursor, iodocaramiphen, was synthesized from c ommercially available 1-phenylcyclopentanecarboxylic acid with a 10% o verall yield in a 5 step procedure. This synthesis includes the format ion of 1-(p-nitrophenyl)-, 1-(p-aminophenyl)- and 1-(p-iodophenyl) cyc lopentane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotra cer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the polls tissues indicated that there was still 92% of unchanged radiotracer 30 min p.i. After coinjection o f dextrometorphan, a sigma ligand, a reduction of the radioactivity up take by 20 to 27% was observed in the pens, the colter, the striatum a nd the cerebellum. These data suggest that [Br-76]bromocaramiphen is n ot a potential probe for investigating the status of central M(1) musc arinic receptors because of its high lipophilicity (log P-7.4 = 2.4) a nd its affinity for sigma sites.