[C-11]-GR89696, a potent kappa opiate receptor radioligand; in vivo binding of the R and S enantiomers

The R and S enantiomers of [C-11]GR89690, [C-11]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate. were synthesized from their appropriate chiral precursors and [C-11]methyl chloroformate. The [C-11]-labeled R enantiomer of GR89696, also known as GR103545, demonstrated high affinity in mouse brain with region to cerebellar ratios at 90 minutes of 11.4 and 8.7 for the hypothalamus and olfactory tubercle, respectively. The [C-11]-labeled S enantiomer showed low affinity and region to cerebellar ratios of 1 for all brain regions. The [C-11]-labeled GR103545 exhibited a selective and saturable binding for the kappa opioid receptor. (C) 2002 Elsevier Science Inc. All rights reserved.