Neuroleptic activity in 5-aryltetrahydro-gamma-carbolines.
A series of 5-aryltetrahydro-gamma-carbolines was prepared by a novel N-arylation procedure and tested for neuroleptic activity in a rat antiamphetamine model. The systematic exploration of structural parameters leading to 8-fluoro-5-(4-fluorophenyl)-2-[4-hydroxy-4-(4-fluorophenyl)butyl]-2,3,5-tetrahydro-1H-pyrido[4,3-b]indole (CP-36,584, flutroline), a potent and long-acting neuroleptic compound, is described. These semirigid compounds provide a new, structurally distinct series with which to probe the conformational requirements for potent activity at the dopamine receptor.
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D001667:Binding, Competitive; D002243:Carbolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis*; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism; D012995:Solubility; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
D014150:Antipsychotic Agents; D002243:Carbolines; D007211:Indoles; D011954:Receptors, Dopamine; D013134:Spiperone; D003913:Dextroamphetamine