6-Hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine and Analogs: New Centrally Acting 5-HT1A Receptor Agonists

J Med Chem. 1992 Oct 30;35(22):3984-90. doi: 10.1021/jm00100a002.

Abstract

The ring-closed phenylethylamine analogue 6-hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine (1) is a 5-HT1A receptor agonist of moderate potency, according to both in vivo biochemical data and in vitro binding data. The active compounds of this series also induce the 5-HT behavioral syndrome. Molecular modeling studies were performed with molecular mechanics calculations, and a tentative explanation for the relatively low potency of these serotonergic benzazepines is provided.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzazepines / chemistry*
  • Benzazepines / pharmacology*
  • Binding, Competitive
  • Brain / drug effects
  • Brain / metabolism
  • Dopamine / biosynthesis
  • Feedback
  • In Vitro Techniques
  • Male
  • Models, Molecular
  • Molecular Conformation
  • Motor Activity / drug effects
  • Norepinephrine / biosynthesis
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Serotonin / biosynthesis
  • Serotonin Receptor Agonists / chemistry*
  • Serotonin Receptor Agonists / pharmacology*
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • Benzazepines
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin
  • Dopamine
  • Norepinephrine