Potentiation of Morphine Analgesia by Adjuvant Activation of 5-HT7 Receptors

Department of Pharmacology, Drug Discovery and Preclinical Development, Esteve, Spain.
Journal of Pharmacological Sciences (Impact Factor: 2.36). 08/2011; 116(4):388-91. DOI: 10.1254/jphs.11039SC
Source: PubMed


Spinal blockade of 5-HT7 receptors has been reported to inhibit the antinociceptive effect of opioids. In this study, we found that subcutaneous administration of the selective 5-HT7 receptor agonist E-55888 (10 mg/kg) or the antagonist SB-258719 (5 mg/kg) exerted no effect on the tail-flick test in mice. However, E-55888, but not SB-258719, increased (2.6-fold) the analgesic potency of oral morphine. The potentiating effect exerted by E-55888 was prevented by SB-258719. A pharmacokinetic interaction was discarded as morphine plasma and brain concentrations were not significantly modified when co-administered with E-55888. These results reinforce the involvement of 5-HT7 receptors in opioid analgesia and point to a potential use of 5-HT7 receptor agonists as adjuvants of opioid analgesia.

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Available from: José Miguel Vela, Jun 13, 2014
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    • "The lack of antinociceptive effects in thermal and phase I formalin-induced nociception, observed when 5-HT7 receptor agonists were administered, suggests no direct modulation by the 5-HT7 receptor subtype of acute nociceptive signals coming from small caliber unmyelinated nociceptive afferents. However, activation of spinal 5-HT7 receptors has been shown to play a role in the antinociceptive effects of opioids [44–47]. "
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