Stereoselective binding of 11C-labelled piquindone (Ro 22–1319) to dopamine-D2 receptors in the living human brain

1987 
The stereoenantiomers of piquindone (Ro 22–1319), a new antipsychotic pyrroloisoquinoline derivative, were labelled with the positron-emitting isotope 11C. Only the (−)-enantiomer inherits most of the biological activity of racemic piquindone. The compounds were examined by positron emission tomography (PET) for dopamine-D2 receptor binding in the living brain of Cynomolgus monkeys and healthy human subjects. After i.v. administration of tracer doses the (−)-enantiomer but not the (+)-enantiomer was shown to accumulate markedly in the dopamine-D2 receptor rich caudate/putamen in both species. After (−) 11C piquindone injection, radioactivity in the human caudate/putamen, and the putamen/cerebellar activity ratio increased to about 2 during the hour when radioactivity could be followed. (−)11C piquindone binding in the monkey putamen was not easily displaceable by haloperidol. The results demonstrate that (−) but not (+)-11C piquindone has a high affinity for dopamine-D2 receptors in the living human brain. The results are compatible with the view that clinical administration of piquindone produces a long-lasting effect on central dopamine-D2 receptors. (−)11C Piquindone is a useful ligand for visualization of dopamine-D2 receptor binding by PET and for analysing relationships between antipsychotic effects of piquindone and blockade of specific binding sites in the brain of schizophrenic patients.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    14
    References
    11
    Citations
    NaN
    KQI
    []