Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex.
Effect of typical and atypical antipsychotic drugs on 5-HT2 receptor density in rat cerebral cortex.
复制标题
典型和非典型抗精神病药物对大鼠大脑皮层5-HT2受体密度的影响。
DOI：
10.1016/0024-3205(89)90027-1
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发表时间：
1989
期刊：
影响因子：
6.1
通讯作者：
Meltzer,HY
中科院分区：
文献类型：
--
作者：
Matsubara,S;Meltzer,HY
本文研究了七种非典型抗精神病药物和四种典型抗精神病药物急性给药对大鼠大脑皮层5-HT_2受体结合位点的影响。在非典型抗精神病药物中，氯氮平、氟哌拉平、RMI-81582和司托哌隆可降低5-HT 2受体密度，而噻螺酮、安哌齐特和美哌隆则无此作用。所有药物均不影响Kd值。在典型的抗精神病药物中，洛沙丁胺醇降低Bmax，增加5-HT 2受体结合位点的Kd，而氯丙嗪和顺式氟哌噻吨则无此作用。与氯氮平化学类别相同的典型抗精神病药物氯噻呋降低Bmax，但不增加Kd。单次注射20 mg/kg氯氮平后，5-HT 2受体结合位点的下调在最初72小时内几乎保持不变，并在长达120小时内仍显着降低。下调大鼠皮层5-HT 2受体结合位点的亲和力与5-HT 2受体密度无关。同时给予D1多巴胺受体激动剂SKF-38393，不影响氯氮平诱导的下调。这表明，5-HT 2受体位点的快速和长期下调是一些非典型抗精神病药物的特征，但不是所有非典型抗精神病药物的特征，也不是非典型抗精神病药物的特异性。二苯卓类药物（氯氮平、洛沙坦、阿莫西林、噻托溴铵）在急性治疗后持续下调额叶皮质5-HT 2受体。
The effect of acute treatment with seven atypical antipsychotic drugs and four typical antipsychotic drugs on serotonin2(5-HT2) receptor binding sites in rat cerebral cortex was studied. Among the atypical antipsychotic drugs examined, clozapine, fluperlapine, RMI-81582 and setoperone decreased the density of 5-HT2receptors, but tiospirone, amperozide and melperone did not. None of the drugs affected the Kdvalue. Among the typical antipsychotic drugs, loxapine decreased Bmaxand increased the Kdof 5-HT2receptor binding sites, whereas chlorpromazine and cis-flupenthixol had no effect. Clothiapine, a typical antipsychotic drug of the same chemical class as clozapine, decreased Bmaxwithout increasing Kd. The downregulation of 5-HT2receptor binding sites following a single injection of clozapine, 20 mg/kg, remained almost unchanged during the first 72 hrs and was still significantly decreased for up to 120 hrs. There was no relationship between the affinity for the downregulation of rat cortical 5-HT2receptor binding site and 5-HT2receptor density. Coadministration of the D1dopamine agonist, SKF-38393, did not affect the clozapine-induced downregulation. It is suggested that rapid and prolonged downregulation of 5-HT2receptor sites is characteristic of some but not all atypical antipsychotic drugs and is not specific to atypical antipsychotic drugs. Dibenzo-epines (clozapine, loxapine, amoxapine, chlothiapine) consistently downregulate 5-HT2receptors in frontal cortex after acute treatment.