Resolved N,N-dialkylated 2-amino-8-hydroxytetralins: stereoselective interactions with 5-HT1A receptors in the brain.
The enantiomers of the N,N-dimethylamino (1), N,N-diethylamino (2), and N,N-dibutylamino (4) derivatives of 8-hydroxy-2-(dipropylamino)tetralin (8-OH DPAT; 3) have been synthesized. The compounds have been tested for activity at central 5-hydroxytryptamine and dopamine receptors by use of biochemical and behavioral tests in rats. In addition, the ability of the enantiomers of 1-4 to displace [3H]-8-OH DPAT from 5-HT1A binding sites was evaluated. Rank order of potencies in the in vivo tests corresponded to that observed in the 5-HT1A binding assay. In all three tests, the enantiomeric potency ratio was about 10 for 1 and 2 and only around 2-4 for 3 and 4. The more potent enantiomer of 1-3 had the R configuration. In contrast, (S)-4 seemed to be slightly more potent than (R)-4.
Björk
L
L
Department of Medical Pharmacology, Uppsala Biomedical Center, University of Uppsala, Sweden.
Höök
B B
BB
Nelson
D L
DL
Andén
N E
NE
Hacksell
U
U
D006916:5-Hydroxytryptophan / Q000096:biosynthesis; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis; D004298:Dopamine / Q000096:biosynthesis; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000096:biosynthesis; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*
D009281:Naphthalenes; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D012701:Serotonin; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006916:5-Hydroxytryptophan; D004298:Dopamine