Structure-activity relationship studies of central nervous system agents. 13. 4-[3-(Benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine, a new putative 5-HT1A receptor antagonist, and its analogs

J Med Chem. 1994 Aug 19;37(17):2754-60. doi: 10.1021/jm00043a014.

Abstract

A new set of 4-alkyl-1-(o-methoxyphenyl)piperazines containing a terminal benzotriazole fragment were synthesized, and their 5-HT1A and 5-HT2 affinity was determined. It was shown that the benzotriazole moiety contributes to both the 5-HT1A and 5-HT2 receptor affinity. It was demonstrated in several behavioral models that 4-[3-(benzotriazol-1- yl)propyl]-1-(2-methoxyphenyl)piperazine (11) is a new, potent presynaptic and postsynaptic 5-HT1A receptor antagonist. However, it is not selective for 5-HT1A versus alpha 1 receptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Body Temperature Regulation / drug effects
  • Brain / metabolism*
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology*
  • Posture*
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin, 5-HT1
  • Reserpine / pharmacology
  • Serotonin Antagonists*
  • Stereotyped Behavior / drug effects
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Indicators and Reagents
  • Piperazines
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Triazoles
  • 4-(3-(benzotriazol-1-yl)propyl)-1-(2-methoxyphenyl)piperazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Reserpine