Synthesis and in vivo evaluation of (E)-N-[(11)C]Methyl-4- (3-pyridinyl)-3-butene-1-amine ([(11)C]metanicotine) as a nicotinic receptor radioligand.

(E)-N-[(11)C]Methyl-4-(3-pyridinyl)-3-butene-1-amine ([(11)C]metanicotine), a high affinity (K(i) = 16 nM) CNS-selective nicotinic agonist, was prepared by the [(11)C]alkylation of the desmethyl precursor with [(11)C]methyl trifluoromethanesulfonate. In vivo distribution studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distribution and no evidence of specific binding to nicotinic cholinergic receptors. Identical results were obtained in an imaging study performed in a monkey brain. Therefore, despite literature reports supporting the use of metanicotine as a cognition enhancing nicotinic agonist, (E)-N-[(11)C]methyl-4-(3-pyridinyl)-3-butene-1-amine does not appear to be a suitable candidate for in vivo imaging studies of nicotinic acetylcholine receptors in the mammalian brain.