The effects of ifenprodil on the activity of antidepressant drugs in the forced swim test in mice

Pharmacol Rep. 2014 Dec;66(6):1031-6. doi: 10.1016/j.pharep.2014.06.016. Epub 2014 Jun 30.

Abstract

Background: According to reports in the literature, more than 30% of depressive patients fail to achieve remission. Therapy with the conventional antidepressant drugs may induce the serious adverse reactions. Moreover, its benefits may be seen at least 2-4 weeks after the first dose. Therefore, the alternative strategies for prevention and treatment of depression are sought. The main aim of our study was to assess the effects of ifenprodil given at a non-active dose (10mg/kg) on the activity of antidepressant agents from diverse pharmacological groups.

Methods: The antidepressant-like effect was assessed by the forced swim test in mice.

Results: Ifenprodil potentiated the antidepressant-like effect of imipramine (15mg/kg) and fluoxetine (5mg/kg) while did not reduce the immobility time of animals which simultaneously received reboxetine (2.5mg/kg) or tianeptine (15mg/kg).

Conclusion: The concomitant administration of certain commonly prescribed antidepressant drugs that affect the serotonergic neurotransmission (i.e., typical tricyclic antidepressants and selective serotonin reuptake inhibitors) with a negative modulator selectively binding to the GluN1/N2B subunits of the NMDA receptor complex (i.e., ifenprodil) may induce a more pronounced antidepressant-like effect than monotherapy. However, these findings still need to be confirmed in further experiments.

Keywords: Antidepressant-like activity; Forced swim test; Ifenprodil; Mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Depression / drug therapy*
  • Disease Models, Animal
  • Drug Synergism
  • Fluoxetine / administration & dosage
  • Fluoxetine / pharmacology
  • Imipramine / administration & dosage
  • Imipramine / pharmacology
  • Mice
  • Morpholines / administration & dosage
  • Morpholines / pharmacology
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Reboxetine
  • Swimming
  • Thiazepines / administration & dosage
  • Thiazepines / pharmacology

Substances

  • Antidepressive Agents
  • Morpholines
  • Piperidines
  • Thiazepines
  • Fluoxetine
  • tianeptine
  • Reboxetine
  • Imipramine
  • ifenprodil