Bioactive conformation of 1-arylpiperazines at central serotonin receptors

J Med Chem. 1985 Jul;28(7):945-8. doi: 10.1021/jm00145a017.

Abstract

A number of 1-arylpiperazines have been characterized as direct-acting serotonin agonists. Conformational parameters of this class that may affect receptor recognition and binding have been examined through the analysis of X-ray data and synthesis of rigid analogues. Radioligand binding studies indicate that 2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino[1,2-a]quinoline, an arylpiperazine that mimics the X-ray conformation of the serotonin agonist 1-(6-chloropyrazin-2-yl)piperazine, exhibits high affinity for serotonin receptors, suggesting that the two rings of 1-arylpiperazines are relatively coplanar in the bioactive conformation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Central Nervous System / drug effects
  • Central Nervous System / physiology
  • Chemical Phenomena
  • Chemistry
  • Female
  • Frontal Lobe / metabolism
  • Mice
  • Molecular Conformation
  • Piperazines / chemical synthesis
  • Piperazines / metabolism*
  • Piperazines / pharmacology
  • Posture
  • Pyrazines / chemical synthesis
  • Pyrazines / metabolism
  • Pyrazines / pharmacology
  • Quinolines / chemical synthesis
  • Quinolines / metabolism
  • Quinolines / pharmacology
  • Rats
  • Receptors, Serotonin / metabolism*
  • Serotonin / metabolism
  • Serotonin / pharmacology
  • Spiperone / metabolism
  • Structure-Activity Relationship

Substances

  • Piperazines
  • Pyrazines
  • Quinolines
  • Receptors, Serotonin
  • Serotonin
  • Spiperone
  • 6-chloro-2-(1-piperazinyl)pyrazine
  • 2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino(1,2-a)quinoline