Buprenorphine及其長效酯Buprenorphine Benzoate在大白鼠之止痛效用測試

The Antinociceptive Effect of Buprenorphine and Its Long-acting Ester Buprenorphine Benzoate in Rats

背景：當病人有長期的疼痛時，長效止痛劑是有需求的。為了延長一強效之止痛劑buprenorphine，我們合成了一個buprenorphine酯(buprenorphine benzoate)。本研究之目的在研究這個酯有無長效作用。方法：我們進行二項實驗，實驗一：我們測量buprenrophine HCI 0.05, 0.1及0.6 μmol/kg之止痛效果。實驗二：我們測量buprenorphine benzoate 0.6 μmol/kg之止痛效果。我們使用雄性Sprague-Dawley鼠（在同一藥物，同一劑量下，每組12隻鼠），並以紅外線熱源(plantar test)來偵測藥物之止痛效用。結果：大白鼠肌肉注射buprenorphine HCI 0.05，0.1，及0.6 μmol/kg可產生3，4，及4小時的止痛效果。大白鼠肌肉注射buprenorphine benzoate 0.6 μmol/kg可產生48小時的止痛效果。結論：在大白鼠以肌肉注射buprenorphine benzoate可產生一個非常長的止痛作用，其效果為buprenorphine HCI的12倍。

Background: A long-acting analgesic is particularly desirable in patients with long-lasting pain. In order to prolong the duration of action of a potent analgesic, buprenorphine, a buprenorphine ester (buprenorphine benzoate) was synthesized in our laboratory. The aim of the study was to evaluate whether the ester form could have a long-lasting effect. Methods: Two studies were carried out. In study 1, we evaluated the antinociceptive effect of buprenorphine HCI at dosage of 0.05, 0.1, and 0.6 μmol/kg. In study 2, we evaluated the antinociceptive effect of buprenorphine benzoate at dosage of 0.6μ mol/kg. Male Sprague-Dawley rats (n = 12 in each group of different treatment) were used and the antinociceptive effects of the testing compounds were evaluated using the plantar test (a thermal test). Results: Intramuscular injection of buprenorphine HCI at dosage of 0.05, 0.1, and 0.6 μmol/kg in rats produced dose-related antinociceptive effects with duration of action of 3, 4, and 4 h, respectively. Intramuscular injection of buprenorphine benzoate at 0.6 μmol/kg produced a duration of action of 48 h. Conclusions: Intramuscular injection of buprenorphine benzoate in rats produced a longer duration of action, which is 12-fold longer than that of buprenorphine HCI.