(S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1- carbaldehyde: a new class of orally active 5-HT1A-receptor agonists.
The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8- amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.
Stjernlöf
P
P
Department of Pharmacology, University of Göteborg, Sweden.
Gullme
M
M
Elebring
T
T
Andersson
B
B
Wikström
H
H
Lagerquist
S
S
Svensson
K
K
Ekman
A
A
Carlsson
A
A
Sundell
S
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001682:Biological Availability; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007211:Indoles; D017366:Serotonin Receptor Agonists; C082404:8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz(e)indole-1-carbaldehyde; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin