Assis Lara C, Scaini Giselli, Di-Pietro Priscila B, Castro Adalberto A, Comim Clarissa M, Streck Emilio L, Quevedo João
Laboratory of Experimental Physiopathology, Postgraduate Programme in Health Sciences, University of Extremo Sul Catarinense, Criciúma, SC, Brazil.
Basic Clin Pharmacol Toxicol. 2007 Nov;101(5):315-9. doi: 10.1111/j.1742-7835.2007.00128.x.
Typical and atypical antipsychotic drugs have different clinical and behavioural profiles. It is well described that inhibition of creatine kinase activity has been implicated in the pathogenesis of a number of diseases, especially in the brain. In this work, we evaluate the effect of haloperidol, clozapine, olanzapine or aripiprazole chronic administration on creatine kinase activity in brain of rats. Adult male Wistar rats received daily injections of haloperidol (1.5 mg/kg), clozapine (25 mg/kg), olanzapine (2.5, 5 or 10 mg/kg) or aripiprazole (2, 10 or 20 mg/kg). Our results demonstrate that haloperidol did not affect the enzyme activity in brain of rats. Clozapine inhibited the enzyme activity only in cerebellum and prefrontal cortex of rats. Aripiprazole did not affect creatine kinase in hippocampus, cerebellum and prefrontal cortex. The administration of 2.0 mg/kg aripiprazole did not alter creatine kinase activity, but 10.0 and 20.0 mg/kg aripiprazole activated the enzyme in striatum and cerebral cortex. Finally, the higher dose of olanzapine (10.0 mg/kg) activated the enzyme in striatum of rats. In hippocampus and cerebral cortex, we could not verify any effect of olanzapine on creatine kinase activity. The inhibitory effect of clozapine and olanzapine on creatine kinase activity in cerebellum and prefrontal cortex suggest that these drugs may impair energy metabolism in these brain areas.
典型和非典型抗精神病药物具有不同的临床和行为特征。已有充分描述表明,肌酸激酶活性的抑制与多种疾病的发病机制有关,尤其是在大脑中。在这项研究中,我们评估了氟哌啶醇、氯氮平、奥氮平或阿立哌唑长期给药对大鼠脑中肌酸激酶活性的影响。成年雄性Wistar大鼠每日注射氟哌啶醇(1.5毫克/千克)、氯氮平(25毫克/千克)、奥氮平(2.5、5或10毫克/千克)或阿立哌唑(2、10或20毫克/千克)。我们的结果表明,氟哌啶醇不影响大鼠脑中的酶活性。氯氮平仅抑制大鼠小脑和前额叶皮质中的酶活性。阿立哌唑不影响海马体、小脑和前额叶皮质中的肌酸激酶。给予2.0毫克/千克阿立哌唑不会改变肌酸激酶活性,但10.0和20.0毫克/千克阿立哌唑会激活纹状体和大脑皮质中的该酶。最后,较高剂量的奥氮平(10.0毫克/千克)激活了大鼠纹状体中的酶。在海马体和大脑皮质中,我们未发现奥氮平对肌酸激酶活性有任何影响。氯氮平和奥氮平对小脑和前额叶皮质中肌酸激酶活性的抑制作用表明,这些药物可能会损害这些脑区的能量代谢。