Department of Zoology, University of Allahabad, Allahabad-211002, India.
Eur J Pharmacol. 2010 May 25;634(1-3):170-7. doi: 10.1016/j.ejphar.2010.02.014. Epub 2010 Feb 20.
Body weight gain, sexual/reproductive dysfunction and hematological abnormalities are serious consequences of atypical antipsychotics treatment. No attempts however have been made preclinically to elucidate the adverse hematological impacts. Presently, effects of lactational exposure of olanzapine (4, 8 and 10 mg/kg) and risperidone (1 and 2 mg/kg) on hematology as well as lymphoid organ histopathology of mice neonates were investigated. Both olanzapine and risperidone transfers through milk and make the neonates susceptible to their adverse side effects. Corticosterone elevation tendency of both the drugs further enhance the susceptibility for immune dysfunction. Analysis of total and differential leukocytes counts revealed neutropenia with all the doses of olanzapine but only with risperidone 2mg/kg. Weight analysis and histopathology of thymus and spleen indicated a state of suppression; less in the risperidone-exposed groups. Significant plasma corticosterone elevation occurred on 4 and 8 mg/kg olanzapine exposures but not with 10 mg/kg as well as with both the risperidone doses. Elevation of plasma prolactin levels occurred dose-dependently for both the drugs. Hematological toxicity (neutropenia) might be the direct toxic effects of the drugs/unstable metabolites on circulating neutrophils and/or on the bone marrow hemopoietic cells. Direct toxicity of the drugs might also have suppressed the lymphoid organs thymus and spleen. Further, it could be associated to hormonal imbalance induced by adverse pharmacological effects of the drugs on the endocrine system. Suppression of lymphoid organs in olanzapine groups might have resulted because of corticosteronemia and hyperprolactinemia, while in risperidone it could be mediated by pronounced hyperprolactinemic effect alone.
体重增加、性功能障碍和血液异常是使用非典型抗精神病药物治疗的严重后果。然而，目前尚未在临床前阶段阐明其对血液系统的不良影响。目前，研究了奥氮平（4、8 和 10mg/kg）和利培酮（1 和 2mg/kg）在哺乳期暴露于小鼠新生儿血液学和淋巴器官组织病理学方面的影响。奥氮平和利培酮都通过乳汁传递，使新生儿易受其不良反应影响。两种药物的皮质酮升高趋势进一步增加了免疫功能障碍的易感性。总白细胞和分类白细胞计数的分析显示，所有奥氮平剂量都出现中性粒细胞减少症，但只有利培酮 2mg/kg 才会出现。胸腺和脾脏的体重分析和组织病理学表明存在抑制状态；利培酮暴露组的抑制程度较低。在奥氮平 4mg/kg 和 8mg/kg 暴露时，显著升高了血浆皮质酮水平，但在 10mg/kg 以及两种利培酮剂量时没有升高。两种药物的血浆催乳素水平均呈剂量依赖性升高。血液毒性（中性粒细胞减少症）可能是药物/不稳定代谢物对循环中性粒细胞和/或骨髓造血细胞的直接毒性作用。药物的直接毒性也可能抑制了淋巴器官胸腺和脾脏。此外，这可能与药物对内分泌系统的不良药理作用引起的激素失衡有关。奥氮平组的淋巴器官抑制可能是由于皮质酮血症和高催乳素血症引起的，而利培酮组则可能是由于明显的高催乳素血症单独介导的。
