| 15056861 |
Sasaki S, Kurosaki F, Haradahira T, Yamamoto F, Maeda J, Okauchi T, Suzuki K, Suhara T, Maeda M: Synthesis of 11C-labelled bis (phenylalkyl) amines and their in vitro and in vivo binding properties in rodent and monkey brains. Biol Pharm Bull. 2004 Apr;27(4):531-7.
Two new (11) C-labelled ligands, N-(3-(4-hydroxyphenyl) propyl)-3-(4-methoxyphenyl) propylamine ([(11) C] 2) and N-(3-(4-hydroxyphenyl) butyl)-3-(4-methoxyphenyl) butylamine ([(11) C] 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 [(11) C] methyl iodide was readily accomplished. The in vitro inhibition experiments using rat brain slices showed that [(11) C] 2 and [(11) C] 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 Zn (2+) produced significant inhibition of both [(11) C] 2 and [(11) C] 3 bindings. Intravenous injection of [(11) C] 3 in mice showed almost homogeneous distribution throughout the brain. Attempts to block the tracer uptake of [(11) C] 3 by pre-injection with the unlabelled 3 or spermine in rats were unsuccessful, but a small decrease in the cerebral uptake of [(11) C] 3 by co-treatment with the unlabelled 3 was observed in a monkey PET study. The present findings indicate that none of these (11) C-labelled analogues have potential for PET study of binding sites on the N-methyl-D-aspartate (NMDA) receptors. |
82(1,1,1,2) |