一個新的長效止痛劑：Bujjrenorphine Palmitate 在大白鼠之測試

A Novel Long-acting Analgesic: Buprenorphine Palmitate in Rats

背景：當病人有長期的疼痛時，長效止痛劑是有需求的。為了長效止痛的目的，我們合成了 一個新的buprenorphine酯類，buprenorphine棕櫚酸酯，本研究的目的在研究這個酯有無長效作 用。方法：我們以plantar test在數種劑量下以大白鼠來偵測傳統止痛劑buprenorphine HC1及新化合物 buprenorphine棕櫚酸酯之止痛作用。結果：我們發現在大白鼠肌肉注射buprenorphine HC1 0.05，0.1及1 jamol/kg可產生和劑量相關之 2，3及4小時之止痛療效。而在大白鼠肌肉注射buprenorphine棕櫚酸酯可產生和劑量相關之 72，76及78小時之止痛效果。在相同的給藥劑量（同莫耳數，1 jimol/kg）下，buprenorphine HC1及 buprenorphine棕櫚酸酯之止痛效期為4及72小時。結論：在大白鼠肌肉注射buprenorphine棕櫚酸酯產生了一個長效的止痛作用，其效期是bupren-orphine HC1的18倍。

Background: A long-acting analgesic may be particularly desirable in patients with long-lasting pain. In order to provide a long-acting analgesic effect, a novel buprenorphine ester, buprenorphine palmitate, was synthesized in our laboratory. The aim of the study was to evaluate whether the ester had a long-lasting effect. Methods: The antinociceptive effects (dose-range studies) of buprenorphine HC1 and buprenorphine palmitate were evaluated using the plantar test in Sprague-Dawley rats. Results: We found that intramuscular injection of buprenorphine HC10.05, 0.1 and 1 ^mol/kg in rats produced dose-related antinociceptive effects of 2, 3, and 4 h, respectively. Intramuscular injection of buprenorphine pal-mitate 1, 5, and 10 ^mol/kg also produced dose-related antinociceptive effects of 72, 76 and 78 h, respectively. On an equimolar basis of 1 ^mol/kg, the durations of action of intramuscular buprenorphine HC1 and buprenorphine palmitate were 4 and 72 h, respectively. Conclusions: Intramuscular injection of buprenorphine palmitate in rats produced a long-lasting antinocicep-tive effect which was much longer (18-fold) than did intramuscular buprenorphine HC1.