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.
Cannon
J G
JG
Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52246.
Moe
S T
ST
Long
J P
JP
D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001060:Aporphines; D011985:Receptors, Serotonin