clozapine and flutroline

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.

Topics: Animals; Carbolines; Chemical Phenomena; Chemistry; Dextroamphetamine; Male; Mice; Molecular Conformation; Rats; Rats, Inbred Strains; Receptors, Dopamine; Spiperone; Stereoisomerism; Stereotyped Behavior; Structure-Activity Relationship