Schulman D S, Kaufman J J, Eisenstein M M, Rapoport S I
Anesthesiology. 1984 Nov;61(5):540-3. doi: 10.1097/00000542-198411000-00011.
14C-Morphine was injected iv in control awake rats or in rats subjected to metabolic alkalosis or acidosis. Ten minutes later, radioactivity was determined within each of seven brain regions, after correction was made for intravascular tracer. In each region, parenchymal radioactivity was correlated positively and significantly (P less than 0.05) with arterial blood pH. Brain radioactivity was twofold to threefold greater in alkalotic rats (mean pH = 7.62) than in acidotic rats (mean pH = 7.16). The results are consistent with the pH-partition hypothesis for drug entry into the brain and indicate that morphine uptake can be increased by elevating the fraction of lipid-soluble uncharged morphine base in blood, by means of alkalosis. The observations may account for an exaggerated morphine-induced analgesia in alkalotic patients.
给清醒的对照大鼠或处于代谢性碱中毒或酸中毒状态的大鼠静脉注射14C-吗啡。十分钟后，在校正血管内示踪剂后，测定七个脑区中每个脑区的放射性。在每个区域，实质放射性与动脉血pH呈显著正相关（P<0.05）。碱中毒大鼠（平均pH = 7.62）的脑放射性比酸中毒大鼠（平均pH = 7.16）高两到三倍。这些结果与药物进入大脑的pH分配假说一致，表明碱中毒可通过提高血液中脂溶性非离子化吗啡碱的比例来增加吗啡的摄取。这些观察结果可能解释了碱中毒患者中吗啡诱导的镇痛作用增强的原因。
