McQuay Henry J, Sullivan Ann F, Smallman Karen, Dickenson Anthony H
Department of Pharmacology, University College, LondonU.K. Nuffield Department of Anaesthetics, Radcliffe Infirmary, OxfordU.K. Division of Anaesthesia, Clinical Research Centre, Northwick ParkU.K.
Pain. 1989 Jan;36(1):111-115. doi: 10.1016/0304-3959(89)90118-8.
To determine the relationship between potency and lipophilicity for intrathecal opioids, morphine, normorphine, pethidine and methadone were studied in an electrophysiological model in the rat. Dose-response curves were constructed for the opioid effects on C fibre evoked activity of dorsal horn nociceptive neurones following intrathecal application of each opioid, and the ED50 values were correlated with lipid solubility. A significant inverse correlation was found (P = 0.002; r = 0.998) so that the most lipid soluble drugs were the least potent. The possible mechanism of this relationship, the implications for spinal opioid use and the effect of different administration routes on the relationship between lipid solubility and potency are considered.
为了确定鞘内注射阿片类药物的效价与亲脂性之间的关系，在大鼠的电生理模型中研究了吗啡、去甲吗啡、哌替啶和美沙酮。在鞘内注射每种阿片类药物后，构建了阿片类药物对背角伤害性神经元C纤维诱发活动影响的剂量-反应曲线，并且将半数有效剂量（ED50）值与脂溶性相关联。发现了显著的负相关（P = 0.002；r = 0.998），因此脂溶性最高的药物效价最低。文中考虑了这种关系的可能机制、脊髓阿片类药物使用的意义以及不同给药途径对脂溶性与效价之间关系的影响。
