Structure-activity relationship studies of CNS agents. Part 9: 5-HT1A and 5-HT2 receptor affinity of some 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines.
The 5-HT1A and 5-HT2 receptor affinity of 2- and 3-substituted 1,2,3,4-tetrahydro-beta-carbolines 1-8, 10 and 12-15 has been determined. It has been found that the specific 5-HT1A affinity of the protonated form (KiAH+) 2-n-hexyl derivatives 4, 8, 14 and (+)-LSD is of the same order. It has been shown by means of molecular modelling methods that pharmacophores of all the active compounds can adopt a common position at the 5-HT1A receptor model. The model also offers an explanation for the observed stereoselectivity chiral compounds.
Bojarski
A J
AJ
Department of Organic Chemistry, Nicolaus Copenicus Academy of Medicine, Kraków, Poland.
Cegła
M T
MT
Charakchieva-Minol
S
S
Mokrosz
M J
MJ
Maćkowiak
M
M
Misztal
S
S
Mokrosz
J L
JL
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002243:Carbolines; D011985:Receptors, Serotonin; D012701:Serotonin; C009804:tryptoline; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin