Maj J, Melzacka M, Mogilnicka E, Daniel W
J Neural Transm. 1982;54(3-4):219-28. doi: 10.1007/BF01254931.
Two schedules of imipramine (IM) administration were compared, a single intraperitoneal dose (10 mg/kg) (I) and chronic oral dosage (10 mg/kg twice a day for 14 days) (II). During schedule I, IMI reached maximal concentration in brain twice as high as that of its metabolite, desipramine (DMI), but disappeared more rapidly. During schedule II, DMI achieved concentrations twice as high as those of IMI which were maintained in a long-lasting plateau and there were considerable differences in areas of brain concentration curves. During schedule I, depletion of brain noradrenaline (NA) induced by H77/77 and of 5-hydroxytryptamine (5-HT) by p-chloro-amphetamine, were inhibited. During schedule II, after DMI concentration had become high and that of IMI low, only NA depletion but not that of 5-HT, was inhibited. At the same time, fenfluramine-induced hyperthermia was not antagonized although it was inhibited in schedule I. These findings may be relevant to those obtained clinically and may help to shed light on mechanisms of antidepressant action.
比较了两种丙咪嗪（IM）给药方案，单次腹腔注射剂量（10mg/kg）（方案I）和慢性口服给药（每天两次，每次10mg/kg，共14天）（方案II）。在方案I期间，IMI在脑中达到的最大浓度是其代谢产物去甲丙咪嗪（DMI）的两倍，但消失得更快。在方案II期间，DMI达到的浓度是IMI的两倍，且维持在一个持久的平台期，脑浓度曲线的面积存在显著差异。在方案I期间，H77/77诱导的脑去甲肾上腺素（NA）耗竭和对氯苯丙胺诱导的5-羟色胺（5-HT）耗竭均受到抑制。在方案II期间，当DMI浓度升高而IMI浓度降低后，仅NA耗竭受到抑制，而5-HT耗竭未受抑制。同时，尽管芬氟拉明诱导的体温过高在方案I中受到抑制，但在方案II中未被拮抗。这些发现可能与临床获得的结果相关，并可能有助于阐明抗抑郁作用的机制。
