Effects of co-administration of a monoamine oxidase inhibitor and a 5-HT1A receptor antagonist on 5-hydroxytryptamine cell firing and release

Eur J Pharmacol. 1997 Feb 5;320(1):15-9. doi: 10.1016/s0014-2999(96)00968-5.

Abstract

We report the effects of the monoamine oxidase inhibitor, tranylcypromine, combined with the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl cyclohexanecarboxamide (WAY 100635), on both 5-hydroxytryptamine (5-HT) cell firing and cortical extracellular 5-HT in the rat. Tranylcypromine inhibited 5-HT cell firing in the dorsal raphe nucleus dose-dependently (ED50 5 mg/kg i.v.). In microdialysis experiments, tranylcypromine (5 mg/kg i.v.) increased extracellular 5-HT in the frontal cortex. WAY 100635 (0.1 mg/kg i.v.) both reversed the inhibition of 5-HT cell firing and facilitated the increase in extracellular 5-HT. In conclusion, WAY 100635 enhances the effect of tranylcypromine on presynaptic 5-HT function. These data are relevant to clinical evidence that co-therapy with a 5-HT1A receptor antagonist improves the antidepressant efficacy of a monoamine oxidase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Drug Synergism
  • Electrophysiology
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism
  • Male
  • Microdialysis
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Piperazines / pharmacology*
  • Pyridines / pharmacology*
  • Raphe Nuclei / cytology
  • Raphe Nuclei / drug effects
  • Raphe Nuclei / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology*
  • Tranylcypromine / pharmacology*

Substances

  • Monoamine Oxidase Inhibitors
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Serotonin
  • Tranylcypromine
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide