Partial postsynaptic 5-HT1A agonist properties of the novel stereoselective 8-OH-DPAT analogue (+)cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin, (+)ALK-3.

The present study assessed the pharmacological activity of the stereoisomers of the novel 8-OH-DPAT analogue cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin, ALK-3, at postsynaptic 5-HT1A receptors involved in 5-HT-mediated behaviour. Reserpine-pretreated rats were injected with (+)8-OH-DPAT (0.03-1.0 mg/kg s.c.), (+)ALK-3 (0.3-10.0 mg/kg s.c.) or (-)ALK-3 (3.0-10.0 mg/kg s.c.), and components of the '5-HT behavioural syndrome' were scored. (+8-OH-DPAT dose dependently elicited forepaw treading, flattened body posture and hindlimb abduction. In this respect, (+)ALK-3 was significantly less efficacious although its behavioural action was prevented by pindolol (8 mg/kg s.c.), indicating that it was 5-HT1A receptor mediated. Following pretreatment, (+)ALK-3 dose dependently, but partially, attenuated the effect of (+)8-OH-DPAT. (-)ALK-3 did not elicit 5-HT behaviours per se, and only very weakly antagonized the behavioural actions of (+)8-OH-DPAT at the highest dose tried. Our data indicate that the (+) enantiomer of ALK-3 is a partial but stereoselective agonist at postsynaptic 5-HT1A receptors.