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Differential involvement of opioidergic and serotonergic systems in the antinociceptive activity of N-arachidonoyl-phenolamine (AM404) in the rat: comparison with paracetamol

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Abstract

It is recognized that paracetamol undergoes a metabolic transformation to N-arachydonylphenolamine (AM404), a CB1 receptor ligand and anandamide uptake inhibitor. Using hot-plate and paw pressure tests, we decided to establish whether AM404 may act through opioidergic and serotonergic mechanisms. Thus, we pretreated rats with opioid μ1 (naloxonazine) and κ (MR2266) or 5-HT1A (NAN-190), 5-HT2 (ketanserin), and 5-HT3 (ondansetron) receptor antagonists. We investigated the possible changes in 5-hydroxyindoleacetic acid/serotonin ratio in the frontal cortex and pons. The antinociceptive effect of AM404 (10 mg/kg, intrapertoneally) or paracetamol (400 mg/kg, intrapertoneally) in either test was abolished by naloxonazine or MR2266. Ondansetron prevented AM404 activity; NAN-190 and ketanserin were ineffective. Ketanserin antagonized paracetamol activity; NAN-190 and ondansetron were inactive. AM404 did not change serotonergic activity, while paracetamol decreased serotonin turnover. The diverse antinociceptive potency of the compounds might be explained by the different influence on the serotonergic system, despite a similar involvement of opioidergic one.

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Authors and Affiliations

  1. Sect. of Pharmacology, Department of Biomedical Sciences, University of Modena and Reggio Emilia, Via G.Campi 287, 41100, Modena, Italy

    Valentina Ruggieri, Giovanni Vitale & Maurizio Sandrini

  2. Clinical Pharmacology Unit, University of Modena and Reggio Emilia, Emilia, Italy

    Luigi Alberto Pini

Authors
  1. Valentina Ruggieri
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  2. Giovanni Vitale
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  3. Luigi Alberto Pini
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  4. Maurizio Sandrini
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Correspondence to Giovanni Vitale.

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Ruggieri, V., Vitale, G., Pini, L.A. et al. Differential involvement of opioidergic and serotonergic systems in the antinociceptive activity of N-arachidonoyl-phenolamine (AM404) in the rat: comparison with paracetamol. Naunyn-Schmied Arch Pharmacol 377, 219–229 (2008). https://doi.org/10.1007/s00210-008-0284-9

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