Trazodone is a Potent Agonist at 5-HT2C Receptors Mediating Inhibition of the N-Methyl-d-Aspartate/Nitric Oxide/Cyclic GMP Pathway in Rat Cerebellum1

  1. Manuela Marcoli,
  2. Guido Maura,
  3. Massimo Tortarolo and
  4. Maurizio Raiteri
  1. Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Università di Genova, Viale Cembrano 4, 16148 Genova, Italy

    Abstract

    The effects of trazodone on the cyclic GMP elevation elicited by N-methyl-d-aspartate in rat cerebellar slices were analyzed. Trazodone inhibited in a concentration-dependent manner (EC50 = 0.82 nM) the cyclic GMP response evoked by 0.1 μM N-methyl-d-aspartate. The inhibition was near complete at 10 nM trazodone. The effect of 10 nM trazodone was unaffected by 0.3 μM spiperone or rauwolscine, antagonists with selectivity for the 5-HT(serotonin)2A or the 5-HT2B subtype, respectively, but it was totally prevented by 0.01 μM mesulergine, a 5-HT2A/5-HT2B/5-HT2C receptor antagonist. Trazodone was potently counteracted (IC50 = 2.7 nM) by the selective 5-HT2B/5-HT2C receptor antagonist N-(1-methyl-5-indolyl)-N-(3-pyridil) urea HCl and, less potently (IC50 = 95 nM), by ketanserin, a 5-HT2A/5-HT2C receptor blocker. It is concluded that trazodone behaves as a potent full agonist at the 5-HT2C receptor mediating inhibition of the cerebellar N-methyl-d-aspartate/nitric oxide/cyclic GMP system.

    Footnotes

    • Send reprint requests to: Maurizio Raiteri, Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Viale Cembrano 4, 16148 Genova, Italy. E-mail: M.Raiteri{at}pharmatox.unige.it

    • ↵1 This work was supported by Italian M.U.R.S.T., by “Progetto Nazionale Sclerosi Multipla—Istituto Superiore di Sanita” and by CNR Target Project on “Biotechnology.”

    • Abbreviations:
      5-HT
      5-hydroxytryptamine (serotonin)
      NMDA
      N-methyl-d-aspartate
      DOI
      (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
      SB200646A
      N-(1-methyl-5-indolyl)-N-(3-pyridil) urea HCl
      NO
      nitric oxide
      mCPP
      m-(chlorophenyl)piperazine
      • Received October 7, 1997.
      • Accepted February 23, 1998.
    « Previous | Next Article »Table of Contents

    This Article

    1. JPET June 1, 1998 vol. 285 no. 3 983-986
    1. » Abstract
    2. Full Text
    3. Full Text (PDF)

    Classifications

    Responses

    1. Submit a response
    2. No responses published

    Current Issue

    1. November 2009, 331 (2)
    1. Current Issue
    1. Alert me to new issues of JPET