GW117: A novel serotonin (5-HT2C ) receptor antagonist and melatonin (MT1 /MT2 ) receptor agonist with potential antidepressant-like activity in rodents

CNS Neurosci Ther. 2021 Jun;27(6):702-713. doi: 10.1111/cns.13630. Epub 2021 Mar 1.

Abstract

Aims: To evaluate the antidepressant-like effect of compound GW117 in rodents using in vitro binding and uptake assays as well in vivo behavioral tests.

Methods: We investigated the target profile of GW117 using [35 S]-GTPγS and [3 H]PIP binding. Using the forced swimming test and chronic unpredictable stress in rats, tail suspension test in mice and rats, and learned helplessness model in mice, we further revealed the antidepressant-like and anxiolytic-like effects of GW117.

Results: The current study suggests that GW117 displays serotonin 2C (5-HT2C ) receptor antagonist and melatonin type 1 and 2 (MT1 /MT2 ) receptor agonist properties, as well as evident antidepressant and anxiolytic effects.

Conclusion: These data suggest that GW117 is probably a potent antidepressant.

Keywords: 5-HT2C receptor; GW117; antidepressant; melatonin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Antidepressive Agents / pharmacology*
  • Helplessness, Learned
  • Hindlimb Suspension
  • Male
  • Mice
  • Mice, Inbred ICR
  • Organic Chemicals / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Melatonin, MT1 / agonists*
  • Receptor, Melatonin, MT2 / agonists*
  • Serotonin 5-HT2 Receptor Antagonists* / pharmacology

Substances

  • Anti-Anxiety Agents
  • Antidepressive Agents
  • GW117
  • Organic Chemicals
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Serotonin 5-HT2 Receptor Antagonists