奥芬太尼对映体的镇痛活性及对阿片受体的选择性

Analgesic activity and selectivity for opioid receptors of enantiomers of ohmefentanyl.

作者信息

Jin W Q, Wang Z X, Chen J, Chen X J, Chi Z Q

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.

出版信息

Zhongguo Yao Li Xue Bao. 1996 Sep;17(5):421-4.

PMID:9863164

Abstract

AIM

To study analgesic activity and selectivity for opioid receptor subtypes of 8 enantomers of ohmefentanyl (Ohm).

METHODS

Analgesic activity was evaluated using the hot plate test in mice. Selectivity for opioid receptors was determined in binding assay and bioassay.

RESULTS

Among the 8 enantiomers of Ohm, the most potent isomer was F-9204, (+)-cis-(3R, 4S, 2'S)-Ohm, with an analgesic ED50 (i.p.) value of 1.1 (0.8-1.3) micrograms.kg-1. These enantiomers selectively acted on mu opioid receptors. Ki values (mu) of enantiomers F-9204 and F-9202, (-)-cis-(3R, 4S, 2'R)-Ohm were 4.0 +/- 2.0 and 5 +/- 4 pmol.L-1, respectively. Their Ki(delta)/Ki(mu) ratios were 22,500 and 22,800, respectively. On guinea pig ileum and mouse vas deferens F-9202, F-9204, F-9205, F-9206, F-9207, and F-9208 exhibited very potent inhibitons, which were antagonized by naloxone. In rabbit vas deferens these enantiomers had no effect.

CONCLUSION

Eight enantiomers of Ohm selectively acted on mu opioid receptors. F-9204 showed the strongest analgesic activity and the highest selectivity for mu opioid receptors.

摘要

目的

研究奥米芬太尼（Ohm）8种对映体的镇痛活性及对阿片受体亚型的选择性。

方法

采用小鼠热板试验评价镇痛活性。通过结合试验和生物测定确定对阿片受体的选择性。

结果

在Ohm的8种对映体中，活性最强的异构体是F-9204，即(+)-顺式-(3R, 4S, 2'S)-Ohm，腹腔注射镇痛ED50值为1.1（0.8 - 1.3）微克·千克⁻¹。这些对映体选择性作用于μ阿片受体。对映体F-9204和F-9202，即(-)-顺式-(3R, 4S, 2'R)-Ohm的Ki值（μ）分别为4.0±2.0和5±4皮摩尔·升⁻¹。它们的Ki(δ)/Ki(μ)比值分别为22,500和22,800。在豚鼠回肠和小鼠输精管上，F-9202、F-9204、F-9205、F-9206,、F-9207和F-9208表现出非常强的抑制作用，可被纳洛酮拮抗。在兔输精管上，这些对映体无作用。