(R)- and (S)-8-acetyl-2-(dipropylamino)tetralin (LY-41): two novel 5-HT1A receptor agonists

Interactions between central 5-HT1A receptors and the enantiomers of LY-41, a 2-aminotetralin derivative related to 8-OH-DPAT (8-hydroxy-2-(dipropylamino)tetralin), were studied. Both enantiomers of LY-41 behaved as potent 5-HT1A receptor agonists in rats, inducing the 5-HT behavioural syndrome, decreasing body temperature and inhibiting the cage-leaving response. The behavioural syndrome and the hypothermia were antagonized by the 5-HT1A receptor antagonist, (S)-UH-301. The LY-41 enantiomers also reduced brain 5-HTP accumulation in rats treated with a decarboxylase inhibitor. The pharmacology of the enantiomers of LY-41 appeared similar to that of 8-OH-DPAT. However, it is noteworthy that the stereoselective interaction of 5-HT1A receptors with LY-41 was opposite to that of 8-OH-DPAT. Thus, (R)-8-OH-DPAT was more potent than (S)-8-OH-DPAT, whereas (S)-LY-41 appeared to be more potent than (R)-LY-41.