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

被引:30
|
作者
Brenchat, Alex [1 ]
Ejarque, Miriam [1 ]
Zamanillo, Daniel [1 ]
Miguel Vela, Jose [1 ]
Romero, Luz [1 ]
机构
[1] Esteve, Dept Pharmacol Drug Discovery & Preclin Dev, Barcelona 08041, Spain
关键词
5-HT7; receptor; analgesia; drug combination; SPINAL; 5-HT7; PAIN;
D O I
10.1254/jphs.11039SC
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:388 / 391
页数:4
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