Nalbuphine及其長效前趨藥Nalbuphine Pivalate在大白鼠之止痛藥效研究

The Analgesic Effect of Nalbuphine and Its Long-acting Prodrug, Nalbuphine Pivalate, in Rats

背景：Nalbuphine是一個具有鴉片接受體拮抗及親合作用的止痛劑。近日來我們已合成了一個Nalbuphine之前趨藥Nalbuphine Pivalate，本研究的目的在評估這前趨藥之止痛效果及效期。方法：將雄性SD鼠分為4組，每組12隻。Nalbuphine HCI製成水溶液且以25 μmol／公斤行大腿肌肉注射。Nalbuphine Pivalate以芝麻油製成油溶液且以25 μmol／公斤行大腿肌肉注射，以上二種劑型之溶液（生理食鹽水及芝麻油）也被用來作為肌肉注射當作對照組。以冰酒精閃尾試驗(-30°C)測試藥物的止痛效果及效期。結果：Nalbuphine HCI及Nalbuphine Pivalate皆有止痛效果，Nalbuphine HCI僅有2小時之止痛效期，而Nalbuphine Pivalate卻有30小時之止痛效期。結論：本研究結果顯示Nalbuphine Pivalate有一個非常長效期的止痛作用，這令人興奮的結果值得我們做更進一步的探討。

Background: Nalbuphine is an opioid-analgesic with agonist-antagonist properties. Recently, we have synthesized a nalbuphine prodrug, nalbuphine pivalate. The aim of the present study was to evaluate the analgesic effect and the analgesic duration of this prodrug. Methods: Forty-eight male Sprague-Dawley rats (4 groups, n = 12 in each group) were used. Rats in group 1 received nalbuphine HCI 25 μmol/kg (in saline) intramuscular injection; rats in group 2 received nalbuphine pivalate 25 μmol/kg (in sesame oil) intramuscular injection, whereas those in groups 3 and 4 received saline and sesame oil respectively. The analgesic effects of testing agents were evaluated using the cold ethanol tail-flick test (-30°C). Results: Both nalbuphine HCI and nalbuphine pivalate demonstrated significant analgesic effects. The analgesic duration of nalbuphine HCI was 2 h while that of nalbuphine pivalate was 30 h. Conclusions: Nalbuphine pivalate has a very long duration of analgesic action. This fascinating finding is worth further evaluation.