Discovery of N-methyl-1-(1-phenylcyclohexyl)methanamine, a novel triple serotonin, norepinephrine, and dopamine reuptake inhibitor

Bioorg Med Chem Lett. 2011 Mar 1;21(5):1438-41. doi: 10.1016/j.bmcl.2011.01.016. Epub 2011 Jan 12.

Abstract

The current work discloses a novel cyclohexylarylamine chemotype with potent inhibition of the serotonin, norepinephrine, and dopamine transporters and potential for treatment of major depressive disorder. Optimized compounds 1 (SERT, NET, DAT, IC(50)=169, 85, 21 nM) and 42 (SERT, NET, DAT IC(50)=34, 295, 90 nM) were highly brain penetrant, active in vivo in the mouse tail suspension test at 30 mpk po and were not general motor stimulants.

MeSH terms

  • Amines / chemical synthesis*
  • Amines / chemistry
  • Amines / pharmacology
  • Animals
  • Antidepressive Agents / chemical synthesis
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / pharmacology
  • Cyclization
  • Dopamine Uptake Inhibitors* / chemical synthesis
  • Dopamine Uptake Inhibitors* / chemistry
  • Dopamine Uptake Inhibitors* / pharmacology
  • Drug Design*
  • Inhibitory Concentration 50
  • Methane / chemical synthesis*
  • Methane / chemistry
  • Methane / pharmacology
  • Mice
  • Molecular Structure
  • Norepinephrine* / chemical synthesis
  • Norepinephrine* / chemistry
  • Norepinephrine* / pharmacology
  • Rats
  • Serotonin* / chemical synthesis
  • Serotonin* / chemistry
  • Serotonin* / pharmacology
  • Stereoisomerism

Substances

  • Amines
  • Antidepressive Agents
  • Dopamine Uptake Inhibitors
  • Serotonin
  • Methane
  • Norepinephrine