Enantiomers of 11-hydroxy-10-methylaporphine having opposing pharmacological effects at 5-HT1A receptors

The two enantiomers of the title compound have been prepared by different synthetic routes. Both bind strongly to 5‐HT1A receptors from rat forebrain membrane tissue. However, in a guinea pig ileum preparation, the (R)‐enantiomer exhibits properties consistent with its being an agonist, whereas the (S)‐enantiomer shows no agonist effect, but it blocks the actions of the (R)‐enantiomer and of 8‐hydroxy‐2‐di‐n‐propylaminotetralin (8‐OH‐DPAT), a 5‐HT1A agonist. These data are presented as a rare example of enantiomers which demonstrate opposite pharmacological effects at the same receptor.