, Volume 122, Issue 4, pp 374–378 | Cite as

Interaction of opioids with antidepressant-induced antinociception

  • F. Sierralta
  • H. F. Miranda
  • G. Pinardi
  • M. Mendez
Original Investigation


The antinociceptive activity of antidepressant drugs is poorly understood. In this study, using the acetic acid writhing test in mice, the antinociception produced by clomipramine (CLO), maprotiline (MAP), imipramine (IMI), and zimelidine (ZIM) was tested and correlated with opioid drugs. All the compounds displayed a significant dose-dependent antinociception, which was not antagonized by naloxone (NX) or naltrexone (NTX). The administration of morphine (M) plus CLO, MAP, IMI or ZIM resulted in a significant additive effect that was antagonized by 1 or 10 mg/kg NX or NTX, except in the case of IMI. This finding suggests that the additive effect seems to be partially due to activation of opioid receptors, except for the case of imipramine. However, aminophylline, a non-selective blocker of A1/A2 adenosine receptors, significantly antagonized the antinociceptive activity of CLO, IMI, MAP and ZIM, demonstrating an interaction at the level of adenosine receptors. This work suggests that the antinociceptive activity of antidepressants could be dependent on critical levels of free 5-HT and NE at receptor(s) site(s) in CNS and on their interaction with opioid and adenosine receptors.

Key words

Antinociception Antidepressants Opioids Adenosine receptors 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • F. Sierralta
    • 1
  • H. F. Miranda
    • 1
  • G. Pinardi
    • 2
  • M. Mendez
    • 2
  1. 1.Department of Pharmacology, Faculty of MedicineUniversidad de ChileSantiagoChile
  2. 2.Department of Experimental Medicine, Campus Occidente, Faculty of MedicineUniversidad de ChileSantiagoChile

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