摘要：Two new 11C-labelled ligands, N -(3-(4-hydroxyphenyl)propyl)-3-(4-methoxyphenyl)propylamine ([11C]2) and N -(3-(4-hydroxyphenyl)butyl)-3-(4-methoxyphenyl)butylamine ([11C]3) were designed based on bis(phenylalkyl)amines (1) which have been reported as polyamine site antagonists with high-selectivity for NR1A/2B NMDA receptors, and radiolabelling of the corresponding phenol precursors with [11C]methyl iodide was readily accomplished. The in vitro inhibition experiments using rat brain slices showed that [11C]2 and [11C]3 share the binding sites with spermine and/or ifenprodil but not with CP-101,606, a highly potent NR2B-selective NMDA antagonist, and that divalent cations such as Zn2+ produced significant inhibition of both [11C]2 and [11C]3 bindings. Intravenous injection of [11C]3 in mice showed almost homogenous distribution throughout the brain. Attempts to block the tracer uptake of [11C]3 by pre-injection with the unlabelled 3 or spermine in rats were unsuccessful, but a small decrease in the cerebral uptake of [11C]3 by co-treatment with the unlabelled 3 was observed in a monkey PET study. The present findings indicate that none of these 11C-labelled analogues have potential for PET study of binding sites on the N -methly- D -aspartate (NMDA) receptors.
关键词：N-methly- D -aspartate (NMDA) receptor antagonist;11C-labelling;brain distribution;inhibition experiment;bis(phenylalkyl)amine;polyamine binding site
