Schizophrenia: Moving beyond monoamine antagonists
Schizophrenia: Moving beyond monoamine antagonists
复制标题
DOI：
10.1124/mi.8.2.7
复制
发表时间：
2008-04-01
影响因子：
--
通讯作者：
Lindsley, Craig
中科院分区：
文献类型：
--
作者：
Conn, P. Jeffrey;Tamminga, Carol;Lindsley, Craig
精神分裂症是一种致残性精神障碍，其特征是阳性、阴性和认知症状。精神分裂症的第一种药物治疗方法是通过偶然的临床观察发现的，尽管有仔细的记录。氯丙嗪和其他多巴胺D-2受体拮抗剂作为抗精神病药物的发现，为精神分裂症和其他精神疾病的药物发现奠定了基础，各种单胺受体成为神经药理学研究的主要焦点。然而，由于在解决阴性症状和认知障碍方面普遍缺乏疗效，治疗阳性症状的成功仍然有限。近年来，出现了几种新的实验方法，用于识别和治疗不依赖于单胺受体阻断的不同症状群。毒蕈碱、烟碱和神经递质信号传导机制已成为精神分裂症离散方面的神经药理学和行为模型所必需的。由于这些见解，新的药物实体已可用于研究和潜在治疗精神疾病的致残性认知和阴性症状。目前靶向一系列新受体的尝试需要对特定受体亚型的药理学操作进行前所未有的微调。
Schizophrenia is a disabling psychiatric disorder characterized by positive, negative, and cognitive symptoms. The first pharmacological treatments for schizophrenia were discovered by serendipitous, albeit carefully documented, clinical observations. The discovery of chlorpromazine and other dopamine D-2 receptor antagonists as antipsychotic agents set the early course of drug discovery in the context of schizophrenia and other psychiatric disorders, and various monoamine receptors became the prime focus of neuropharmacological studies. Success in treating the positive symptoms nevertheless remained limited by the general lack of efficacy in addressing negative symptoms and cognitive impairment. In recent years, several new experimental approaches have emerged for the identification and treatment of different symptom clusters that do not rely on blockade of monoamine receptors. Muscarinic, nicotinic, and glutamatergic signaling mechanisms have become essential to neuropharmacological and behavioral models of discrete aspects of schizophrenia. And as a consequence of these insights, novel drug entities have become available to study and potentially treat the disabling cognitive and negative symptoms of psychiatric disease. Current attempts to target a new range of receptors entail unprecedented fine-tuning in the pharmacological manipulation of specific receptor subtypes.