Tsushima H, Mori M, Matsuda T
Department of Pharmacology, Nagoya City University Medical School, Japan.
Neuropharmacology. 1990 Aug;29(8):757-63. doi: 10.1016/0028-3908(90)90129-f.
The analgesic fentanyl, having a predominantly mu-opioid agonist activity, when injected into the supraoptic or paraventricular nucleus of the hypothalamus in a water-loaded and ethanol-anesthetized rat, induced a potent antidiuretic effect in a time- and dose-dependent manner. The outflow of urine decreased to a minimal level of approximately 5% of the initial control, at 20-40 min and recovered to approximately 80% at 90 min after injection of fentanyl (30 nmol). The median effective dose (ED50) for the antidiuretic effect of fentanyl was approximately 13 nmol, when injected into the supraoptic or paraventricular nucleus, being nearly equipotent with morphine. The osmotic pressure of urine increased up to approximately 200% of control, at the minimal rate of outflow of urine when fentanyl (30 nmol) was injected into the supraoptic or paraventricular nucleus. Transient but significant decreases in mean blood pressure and in rate of respiration were observed when fentanyl (30 nmol) was injected into the supraoptic or paraventricular nucleus. The antidiuretic and the autonomic effects (transient decreases in mean blood pressure and rate of respiration) were inhibited by the previous injection of an opioid receptor antagonist, naloxone (300 or 600 nmol) into the nuclei. The results suggest that the effects of fentanyl were induced through opioid receptors in the nuclei.
具有主要μ-阿片受体激动剂活性的镇痛剂芬太尼，在给经水负荷及乙醇麻醉的大鼠下丘脑视上核或室旁核注射时，会以时间和剂量依赖性方式诱导出强效抗利尿作用。注射芬太尼（30 nmol）后20 - 40分钟，尿量减少至初始对照值的约5%的最低水平，90分钟时恢复至约80%。当注射到视上核或室旁核时，芬太尼抗利尿作用的半数有效剂量（ED50）约为13 nmol，与吗啡几乎等效。当向视上核或室旁核注射芬太尼（30 nmol）使尿量流出率最低时，尿液渗透压增加至对照值的约200%。当向视上核或室旁核注射芬太尼（30 nmol）时，观察到平均血压和呼吸频率出现短暂但显著的下降。预先向核内注射阿片受体拮抗剂纳洛酮（300或600 nmol）可抑制抗利尿作用及自主神经作用（平均血压和呼吸频率短暂下降）。结果表明，芬太尼的作用是通过核内的阿片受体诱导产生的。
