Potentiation of morphine analgesia by adjuvant activation of 5-HT 7 receptors

Spinal blockade of 5-ht 7 receptors has been reported to inhibit the antinociceptive effect of opioids. in this study,we found that subcutaneous administration of the selective 5-ht 7 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-ht 7 receptors in opioid analgesia and point to a potential use of 5-ht 7 receptor agonists as adjuvants of opioid analgesia. © the japanese pharmacological society.