6-Hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine and analogs: new centrally acting 5-HT1A receptor agonists.
The ring-closed phenylethylamine analogue 6-hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine (1) is a 5-HT1A receptor agonist of moderate potency, according to both in vivo biochemical data and in vitro binding data. The active compounds of this series also induce the 5-HT behavioral syndrome. Molecular modeling studies were performed with molecular mechanics calculations, and a tentative explanation for the relatively low potency of these serotonergic benzazepines is provided.
Wikström
H
H
Department of Pharmacology, University of Göteborg, Sweden.
Andersson
B
B
Elebring
T
T
Lagerkvist
S
S
Hallnemo
G
G
Pettersson
I
I
Jovall
P A
PA
Svensson
K
K
Ekman
A
A
Carlsson
A
A
D000818:Animals; D001552:Benzazepines / Q000737:chemistry* / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis; D005246:Feedback; D066298:In Vitro Techniques; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000096:biosynthesis; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis; D017366:Serotonin Receptor Agonists / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D001552:Benzazepines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine