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Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice

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Summary

The putative serotonin (5-HT) receptor antagonist metitepin (0.5 mg/ kg, intraperitoneally) produced hypoalgesia in the increasing temperature hot-plate test and hyperalgesia in the tail-flick test in mice. The effects of metitepin were not altered after depletion of 5-HT by the neurotoxin 5,7-dihydroxytryptamine (5, 7-DHT, 80 Μg free base, intracerebroventricularly) or the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA, 400 mg/kg for 10 consecutive days). After chronic administration (2 or 5 mg/kg for 18 consecutive days) tolerance to the effect of metitepin (0.5 mg/kg) and cross-tolerance to the antinociceptive effect of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 3 mg/kg) was found in the hot-plate test but not in the tail-flick test. It is suggested that metitepin may block descending 5-HT transmission while more complex mechanisms of action are involved at supraspinal level. One possibility is that metitepin exhibits partial agonist properties or, alternatively, that the drug may block 5-HT subsystems which tonically enhance nociception.

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  1. P. K. Eide

    Present address: Department of Physiology, University of Bergen, Bergen, Norway

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  1. Department of Physiology, University of Bergen, Bergen, Norway

    K. Hole & O. -G. Berge

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  1. P. K. Eide
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  2. K. Hole
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  3. O. -G. Berge
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Eide, P.K., Hole, K. & Berge, O.G. Mechanisms by which the putative serotonin receptor antagonist metitepin alters nociception in mice. J. Neural Transmission 73, 31–41 (1988). https://doi.org/10.1007/BF01244620

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  • DOI: https://doi.org/10.1007/BF01244620

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