Neuroleptic activity of chiral trans-hexahydro-gamma-carbolines

J Med Chem. 1986 Jan;29(1):8-19. doi: 10.1021/jm00151a002.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Carbolines / pharmacology*
  • Chemical Phenomena
  • Chemistry
  • Dextroamphetamine / antagonists & inhibitors
  • Male
  • Mice
  • Molecular Conformation
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Spiperone / metabolism
  • Stereoisomerism
  • Stereotyped Behavior / drug effects*
  • Structure-Activity Relationship

Substances

  • Carbolines
  • Receptors, Dopamine
  • Spiperone
  • flutroline
  • Dextroamphetamine