Molecular docking and panicolytic effect of 8-prenylnaringenin in the elevated T-maze

Chem Pharm Bull (Tokyo). 2014;62(12):1231-7. doi: 10.1248/cpb.c14-00569.

Abstract

The purpose of this study was to investigate the effects of the chronic administration of a racemic mixture of 8-prenylnaringenin (8-PN) on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (SERT) reuptake inhibitor fluoxetine was used as a positive control. Rat locomotion was assessed in a circular arena following each drug treatment. The administration of racemic 8-PN for 21 d in rats increased one-way escape latencies from the ETM open arm, indicating a panicolytic effect. To evaluate the interactions of 8-PN with monoamine transporters, a docking study was performed for both the R and S configurations of 8-PN towards SERT, norepinephrine (NET) and dopamine transporters (DAT). The application of the docking protocol showed that (R)-8-PN provides greater affinity to all transporters than does the S enantiomer. This result suggests that enantiomer (R)-8-PN is the active form in the in vivo test of the racemic mixture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / metabolism*
  • Anti-Anxiety Agents / pharmacology*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Flavanones / pharmacology*
  • Fluoxetine / pharmacology
  • Male
  • Models, Molecular
  • Motor Activity / drug effects
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism
  • Panic Disorder / drug therapy
  • Rats
  • Rats, Wistar
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 8-prenylnaringenin
  • Anti-Anxiety Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Flavanones
  • Norepinephrine Plasma Membrane Transport Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Fluoxetine