选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

COMPARISON OF PHARMACOLOGICAL PROFILE OF SELECTIVE κ-OPIOID AGONIST K-Ⅱ AND U-50488

摘要: K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。

Abstract: K-Ⅱ is an analogue of U-50488, a selective κ-opioid agonist. Comparison of pharmacological profile of K-Ⅱ and U-50488 was studied using in vitro and in vivo methods. The results showed that the IC₅₀ values of K-Ⅱ and U-50488 on electrically induced contraction of the rabbit vas deferens were 0.42 nmol/L and 26.5 nmol/L, respectively. ED₅₀ values of K-Ⅱ and U-50488 in impairing motor function of mouse in the horizontal screen test were 1.7 and 15.3 mg/kg, respectively. The effect of K-Ⅱ in reducing spontaneous activity of mouse was 6 times as potent as U-50488. These results suggest that K-Ⅱ is a more potent kappaagonist in pharmacological effects than U-50488.