title: (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.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Göteborg, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Stjernlöf
authors.forename: M
authors.initials: M
authors.lastname: Gullme
authors.forename: T
authors.initials: T
authors.lastname: Elebring
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Wikström
authors.forename: S
authors.initials: S
authors.lastname: Lagerquist
authors.forename: K
authors.initials: K
authors.lastname: Svensson
authors.forename: A
authors.initials: A
authors.lastname: Ekman
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
authors.forename: S
authors.initials: S
authors.lastname: Sundell
mesh_terms: 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
chemical_list: 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