Department of Pharmacology, Drug Discovery and Preclinical Development, Esteve, Spain.
J Pharmacol Sci. 2011;116(4):388-91. doi: 10.1254/jphs.11039sc. Epub 2011 Jul 21.
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.
5-HT7 受体的脊髓阻断已被报道可抑制阿片类药物的镇痛作用。在这项研究中，我们发现皮下给予选择性 5-HT7 受体激动剂 E-55888（10mg/kg）或拮抗剂 SB-258719（5mg/kg）对小鼠的甩尾试验没有影响。然而，E-55888 而不是 SB-258719 增加了（2.6 倍）口服吗啡的镇痛效力。E-55888 发挥的增效作用被 SB-258719 所阻止。由于当与 E-55888 合用时，吗啡的血浆和脑浓度没有显著改变，因此排除了药代动力学相互作用。这些结果加强了 5-HT7 受体在阿片类药物镇痛中的作用，并指出 5-HT7 受体激动剂作为阿片类药物镇痛的辅助剂具有潜在的用途。
