Development of a presynaptic 5-HT1A antagonist

Bioorg Med Chem Lett. 2003 Jan 20;13(2):285-8. doi: 10.1016/s0960-894x(02)00879-x.

Abstract

A new 5-HT(1A) silent antagonist 14 (5-HT(1A) IC(50)=2.2 nM) antagonizes the effects of agonists on reciprocal forepaw treading behavior, on neuronal firing in the rat dorsal raphé, and on 5-HT(1A) release in the raphé and hippocampus. While 14 alone was inactive in the social interaction paradigm, it completely reversed the social interaction activity of the serotonergic compounds (buspirone, 1, and 2).

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Anti-Anxiety Agents / chemical synthesis
  • Anti-Anxiety Agents / pharmacology
  • Brain Chemistry / drug effects
  • Buspirone / pharmacology
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Electroencephalography / drug effects
  • Interpersonal Relations
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Presynaptic / drug effects*
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Receptor Agonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Anxiety Agents
  • Receptors, Presynaptic
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Buspirone