Fujimura A, Sudoh T, Shiga T, Ohashi K, Ebihara A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Life Sci. 1993;52(9):819-24. doi: 10.1016/0024-3205(93)90080-m.
Circadian variations in the adrenergic nervous system have been reported to be altered by chronic treatment with clorgyline, a monoamine-oxidase inhibitor. In the present study, the influence of clorgyline on the chronopharmacology of furosemide, a loop diuretic agent, was examined in rats maintained under conditions of light from 7 am to 7 pm and dark from 7 pm to 7 am. Clorgyline (4 mg/kg/day) or its vehicle alone was infused subcutaneously by osmotic minipumps for 14 days. Furosemide (30 mg/kg) was given orally at 12 am [noon (N)] or 12 pm [midnight (M)]. Urine was collected for 8 hours after the agent, and urinary excretions of sodium and furosemide were determined. Urine volume and urinary excretions of sodium and furosemide were significantly greater at 12 N than at 12 M in the vehicle-infused group of rats. However these administration time-dependent changes in the effects of furosemide and its urinary excretion disappeared in the clorgyline-infused animals. These results suggest that the mode of the diurnal variation in the effects of furosemide is altered by chronic treatment with clorgyline. As chronic clorgyline is considered to disturb the adrenergic nervous system, the present findings are compatible with the hypothesis that this system is involved in the mechanism responsible for the time-dependent change in the effects of furosemide.
据报道，单胺氧化酶抑制剂氯吉兰的长期治疗会改变肾上腺素能神经系统的昼夜节律变化。在本研究中，在上午7点至晚上7点光照、晚上7点至上午7点黑暗的条件下饲养的大鼠中，研究了氯吉兰对袢利尿剂呋塞米时辰药理学的影响。通过渗透微型泵皮下注射氯吉兰（4mg/kg/天）或其溶媒，持续14天。在上午12点[中午（N）]或晚上12点[午夜（M）]口服给予呋塞米（30mg/kg）。给药后收集8小时尿液，测定钠和呋塞米的尿排泄量。在注射溶媒的大鼠组中，上午12点时的尿量、钠和呋塞米的尿排泄量显著高于晚上12点。然而，在注射氯吉兰的动物中，呋塞米作用及其尿排泄的这些给药时间依赖性变化消失了。这些结果表明，氯吉兰的长期治疗改变了呋塞米作用的昼夜变化模式。由于长期使用氯吉兰被认为会干扰肾上腺素能神经系统，目前的研究结果与该系统参与呋塞米作用时间依赖性变化机制的假设一致。
