Neuroleptic activity of chiral trans-hexahydro-gamma-carbolines.
A series of trans-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5, 9b-hexahydro-1H-pyrido[4,3-b]indoles with various N-2 substituents has been prepared and tested for neuroleptic activity [( 3H]spiroperidol binding and amphetamine antagonism). Several members of this series showed exceptional in vivo potency, especially the hydantoin derivatives 27-30. Resolution into the enantiomers showed that neuroleptic activity is associated with the 4aS,9bS absolute configuration. These rigid neuroleptics have been correlated with other rigid neuroleptics [(+)-dexclamol, Ro 22-1319] and can serve to further define the topography of the dopamine receptor.
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002243:Carbolines; D011954:Receptors, Dopamine; D013134:Spiperone; C026240:flutroline; D003913:Dextroamphetamine