DERIVATIVES OF CIS-2-AMINO-8-HYDROXY-1-METHYLTETRALIN - MIXED 5-HT(1A)-RECEPTOR AGONISTS AND DOPAMINE D-2-RECEPTOR ANTAGONISTS

S,2R)-8-Hydroxy-1-methyl-2-(dipropylamino)tetralin [(1S,2R)-3] has bee n previously characterized as a selective and potent but partial 5-HT1 A-receptor agonist. In the present study, we have prepared derivatives of(1S,2R)- and (1R,2S)-3 in which various C8-substituents have been i ntroduced. In addition, the enantiomers of the N-isopropyl-N-n-propyla mino derivative of 3 were prepared. The new derivatives were tested in vivo by use of behavioral and biochemical tests in rats. In addition, the affinity of the compounds was studied by competition experiments with [H-3]-8-OH-DPAT in rat brain tissue. The only new derivative whic h behaved like a selective 5-HT1A-receptor agonist was the C8-carboxam ide derivative (1S,2R)-13. The other active derivatives, including (1S ,2R)-3, have more complicated pharmacological profiles and may be best characterized as mixed 5-HT1A-receptor agonists/dopamine D-2-receptor antagonists.