嗎啡在臨床上使用為強效止痛劑，但其有藥物耐受性 (tolerance) 及成癮性(addiction) 之副作用，而多巴胺的增加或減少影響腦部報償作用。抗精神病 (antipsychotics) 藥物具有阻斷多巴胺 (dopamine) 接受器之藥理作用，推測其具有減輕嗎啡依賴性小鼠之戒斷症狀 (withdrawal) ，本研究的目的在探討一群抗精神病藥物是否能減輕嗎啡依賴性小鼠之戒斷症狀。
本論文將成年雄性小鼠 (ICR) ，連續皮下注射嗎啡三天，使其產生嗎啡身體依賴性 (morphine dependence)，再給予抗精神病藥物中之吩噻嗪類 (phenothiazines)藥物：氟奮乃靜 (fluphenazine)、三氟普魯麻辛 (triflupromazine)、氯苯 (chlorpromazine)、奮乃靜 (perphenazine) 、丙嗪 (promazine) 、硫利達嗪 (thioridazine) 共六種藥物，而後再以那囉克松 (naloxone) 誘導產生嗎啡身體依賴性後的戒斷症狀—跳躍現象，並觀察各種抗精神病藥物抑制此跳躍反應之療效。在二藥物合併共同治療交互作用的實驗中，我們再以氟奮乃靜和丁基原啡因 (buprenorphine) 在相同強度之劑量下進行藥物合併共療之實驗。
在抗精神病藥物吩噻嗪類中，在劑量為0.3 μmol/kg和生理食鹽水組相比較，皆有顯著減輕跳躍次數 (P < 0.05) ，而藥效強度分別為氟奮乃靜> 三氟普魯麻辛> 氯苯> 奮乃靜> 丙嗪> 硫利達嗪，所有藥物在0.03、0.3、3μmol/kg的劑量下，嗎啡戒斷症狀隨劑量的增加而有效降低小鼠跳躍次數。二藥物合併共同治療使用之效果比單獨藥物加倍劑量之效果有顯著差異，為協同作用 (synergism) 。
我們結論抗精神病藥物之吩噻嗪類藥物有減輕嗎啡依賴性小鼠之戒斷跳躍反應，而藥效強度有所不同且氟奮乃靜與丁基原啡因藥物合併共同治療使用之效果比單獨使用時藥物的加倍劑量效果更好。本研究結果可提供將來在臨床治療藥物成癮時有更多的藥物選擇。 Morphine is a clinically potent analgesic with the side effects of physical tolerance and addiction. Some dopamine may affect brain compensation. Antipsychotics which can block the dopamine receptors were applied in the study to assess if they reduced the withdrawal jumping in morphine-dependent mice.
The subjects were adult male mice with morphine dependence via subcutaneous injections of morphine thrice daily for 3 consecutive days. Several phenothiazines including fluphenazine, triflupromazine, chlorpromazine, perphenazine, promazine, and thioridazine were provided before naloxone-induced withdrawal jumping to investigate the morphine-dependent mice. The effect of combining fluphenazine and buprenorphine with the equivalent dose potency was also studied.
The withdrawal jumping in the phenothiazines group at the dose of 0.3 μmol/kg was significantly (P < 0.05) reduced as compared with that in the normal saline group. The drug potency of fluphenazine was highest, followed by triflupromazine, chlorpromazine, perphenazine, promazine and thioridazine at the dose of 0.3 μmol/kg accordingly. The dose-response effect was observed within dose ranges of 0.03, 0.3 and 3 μmol/kg. The effect of reducing jumping by combining fluphenazine and buprenorphine was more significant than that of the double dose of either single drug, suggesting synergistic effects may be obtained by combining antipsychotics and narcotics.
The effect of fluphenazine, triflupromazine, chlorpromazine, perphenazine, promazin and thioridazine on reducing the withdrawal jumping in morphine-dependent mice was clearly observed in the present study. The effect of fluphenazine and buprenorphine after the combination was more significant than that of either single drug with the double dose, indicating the antipsychotics may be potential for clinically treaty drug addictions.
