Abstract
The R and S enantiomers of [(11)C]GR89696, [(11)C]-methyl 4-[(3,4-dichlorophenyl)acetyl]-3-[(1-pyrrolidinyl)methyl]-1-piperazinecarboxylate, were synthesized from their appropriate chiral precursors and [(11)C]methyl chloroformate. The [(11)C]-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 [(11)C]-labeled S enantiomer showed low affinity and region to cerebellar ratios of 1 for all brain regions. The [(11)C]-labeled GR103545 exhibited a selective and saturable binding for the kappa opioid receptor.
MeSH terms
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Adrenergic alpha-Agonists / chemical synthesis
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Adrenergic alpha-Agonists / metabolism*
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Adrenergic alpha-Agonists / pharmacokinetics
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Animals
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Brain / drug effects
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Brain / metabolism*
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Mice
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Morphinans / pharmacology
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Naltrexone / analogs & derivatives*
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Naltrexone / pharmacology
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Narcotic Antagonists / pharmacology
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Piperazines / chemical synthesis
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Piperazines / metabolism*
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Piperazines / pharmacokinetics
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Pyrrolidines / chemical synthesis
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Pyrrolidines / metabolism*
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Pyrrolidines / pharmacokinetics
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Receptors, Opioid, kappa / metabolism*
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Stereoisomerism
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Tissue Distribution
Substances
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Adrenergic alpha-Agonists
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Morphinans
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Narcotic Antagonists
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Piperazines
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Pyrrolidines
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Receptors, Opioid, kappa
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cyprodime
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GR 89696
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Naltrexone
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naltrindole