INVIVO DISTRIBUTION OF AN ANTI-DEPRESSANT DRUG (DMI) IN MALE AND FEMALE RATS
INVIVO DISTRIBUTION OF AN ANTI-DEPRESSANT DRUG (DMI) IN MALE AND FEMALE RATS
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DOI：
10.1007/bf00492213
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发表时间：
1979-01-01
影响因子：
3.4
通讯作者：
SAMUEL, D
中科院分区：
文献类型：
--
作者：
BIEGON, A;SAMUEL, D
I.P.的积累。在雄性和雌性大鼠的脑和肝脏内注射了~3H-地昔帕明(DMI)。女性大脑中的DMI总量是男性大脑中DMI总量的2-4倍。雌性在发情当天DMI含量最高，发情前期最低。在注射了另一种精神活性药物--~3H-氯丙嗪后，这种性别差异没有被发现。在男性和女性中，大脑皮质和尾状核中的DMI水平略高于海马区、隔区和下丘脑。DMI在男性和女性体内累积的药代动力学和剂量依赖性也是相似的。肝脏中的最高水平在不到15分钟内达到，而在大脑中需要30分钟。肝脏的放射性下降速度比大脑快。在40毫克/公斤的剂量范围内，大脑或肝脏中DMI的摄取量不会达到饱和。脑内~3H-DMI含量的性别差异可能是肝微粒体性别依赖性代谢的结果，也可能解释了男性和女性对抗抑郁药物反应的差异。
The accumulation of i.p. injected 3H-desipramine (DMI) in the brain and in the liver was studied in both male and female rats. The total amount of DMI in the brains of females is 2-4 times that found in the brains of males. In females the amount of DMI is highest on the day of estrus and lowest on proestrus. This sex difference was not found following the injections of another psychoactive drug, 3H-chlorpromazine. In both males and females the level of DMI in the cortex and caudate is slightly higher than in the hippocampus, septum and hypothalamus. The pharmacokinetics and dose dependence of the accumulation of DMI are also similar in males and females. Maximal levels are reached in the liver in less than 15 min, whereas in the brain it takes 30 min. The decline of radioactivity in the liver is faster than in brain. There is no saturation in the amount of DMI taken up in brain or liver in the dose range up to 40 mg/kg. The sex difference in the amount of 3H-DMI in brain, which may be the result of sex-dependent metabolism in liver microsomes, may explain the male-female differences in reaction to antidepressants.