Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats.
Effects of antihistamines on 3, 4-methylenedioxymethamphetamine-induced depletion of serotonin in rats.
复制标题
抗组胺药对 3, 4-亚甲二氧基甲基苯丙胺诱导的大鼠血清素消耗的影响。
DOI：
10.1002/(sici)1098-2396(19990901)33:3
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Cadet,JL
中科院分区：
文献类型：
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作者：
Yeh,SY;Dersch,C;Rothman,R;Cadet,JL
本研究探讨了扑尔敏的影响，（CPA，10-25 mg/kg）、苯海拉明（DIPH，20 mg/kg）、曲哌那明（TRIP，20 mg/kg）和吡拉明（PYRI，20 mg/kg）对3，4-亚甲二氧基甲基苯丙胺（MDMA，20 mg/kg × 2）诱导的大鼠脑内高热和吲哚耗竭，对大鼠突触体摄取5-羟色胺和多巴胺的影响，CPA对大鼠脑突触体生物胺转运体的结合亲和力和清除羟自由基的活性。大鼠接受两次注射MDMA、CPA、DIPH、TRIP、PYRI和生理盐水（单独或MDMA与一种抗组胺药联合），间隔6 h，5天后处死。在药物注射之前和之后每小时测量直肠温度，持续13小时。与生理盐水对照组相比，MDMA使大鼠的体温升高，并通过HPLC测定，使大鼠几个脑区的吲哚水平降低。CPA减弱和DIPH对MDMA诱导的高热没有影响，但两者都减弱了吲哚的消耗，而PYRI和TRIP增强了这些作用。CPA抑制[~ 3 H]帕罗西汀和[~ 3 H]尼索西汀与大脑皮层突触体的结合以及[~ 3 H]win 35，428与纹状体突触体的结合。CPA、DIPH、TRIP和PYRI抑制[3 H] 5-羟色胺摄取。CPA，PYRI和TRIP，而不是DIPH，β-羟基自由基。抗组胺药对MDMA诱导的高热和5-羟色胺耗竭的不同影响的可能机制进行了讨论。Synapse 33：207-217，1999年。出版于1999年Wiley利斯公司
This study investigated the effects of chlorpheniramine (CPA, 10–25 mg/kg), diphenhydramine (DIPH, 20 mg/kg), tripelennamine (TRIP, 20 mg/kg), and pyrilamine (PYRI, 20 mg/kg) on 3,4‐methylenedioxymethamphetamine (MDMA, 20 mg/kg × 2)‐induced hyperthermia and depletion of indoles in rat brains, on the uptake of serotonin and dopamine into rat synaptosomes, on the binding affinity of CPA for biogenic amine transporters in the synaptosomes of rat brain, and on the scavenging hydroxyl free radicals activity. Rats were treated with two injections of MDMA, CPA, DIPH, TRIP, PYRI, and saline, alone or in combination of MDMA with one of the antihistamines, 6 h apart and sacrificed 5 days later. Rectal temperature was measured prior to and hourly following the drug injections for 13 h. As compared to saline controls, MDMA increased body temperature and decreased levels of indoles, measured by HPLC, in several brain regions of rats. CPA attenuated and DIPH had no effect on MDMA‐induced hyperthermia, yet both attenuated the depletion of indoles, whereas PYRI and TRIP potentiated these effects. CPA inhibited the binding of [3H]paroxetine and [3H]nisoxetine to the synaptosomes of cerebral cortex and of [3H]win 35,428 to the synaptosomes of striatum. CPA, DIPH, TRIP, and PYRI inhibited [3H]serotonin uptake. CPA, PYRI, and TRIP, but not DIPH, scavenge hydroxyl radicals. Possible mechanisms of the different effects of the antihistamines on MDMA‐induced hyperthermia and depletion of serotonin are discussed. Synapse 33:207–217, 1999. Published 1999 Wiley‐Liss, Inc.