Synthesis and 11C-labelling of two selective high affinity nicotinic cholinergic agonists for evaluation as radioligands for PET studies
✍ Scribed by Frédéric Dolle; Lilian Dolci; Héric Valette; Michel Bottlaender; Denis Fournier; Chantal Fuseau; Françoise Vaufrey; Christian Crouzel
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- French
- Weight
- 692 KB
- Volume
- 38
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
ABT-418 ((S)-3-methyl-5-[l-methyl-2-pyrrolidinyl]isoxazole) and N-methylcytisine (N-methyl-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido-[ I,2-a][ 1,5]diazocin-8-one) are two high affinity nicotinic cholinergic agonists. ABT-418 was synthesized in 7 steps from commercially available (S)-Boc-proline in 35% overall yield. Methylation of commercial cytisine cleanly gave N-methylcytisine. ABT-418 and N-methylcytisine were labelled using ["Cjmethyl iodide by methylation of the corresponding nor-precursors for their in vivo evaluation as positron emission tomography (PET) probes of the nicotinic cholinergic receptors in baboon brain. As for ["Clnicotine, specific binding in vivo could not be demonstrated for ABT-418. Therefore, further experiments are needed to determine the full PET pharmacological profile and the subsequent potential clinical applications of ABT-418 as a tracer for PET experiments. For labelled N-methyl-cytisine, radioactivity in the cerebral cortex and in the blood were similar. Thus, "C-labelled N-methylcytisine does not appear to be a suitable ligand for mapping brain nAChR.