Goldstein J M
Clinical Medicine Group, Zeneca Pharmaceuticals, Wilmington, Delaware 19850, USA.
Drugs Today (Barc). 1999 Mar;35(3):193-210. doi: 10.1358/dot.1999.35.3.533849.
The goal of antipsychotic drug development efforts over the past 10 years has been to develop agents with increased efficacy and safety and fewer of the side effects commonly associated with the older antipsychotic medications. The newer agents, often called atypical antipsychotics, are effective in treating both the positive and negative symptoms of schizophrenia and are associated with fewer neurological- and endocrine-related side effects compared to the older agents. As a result, patients are likely to remain on therapy longer, preventing relapses and costly hospitalizations. Quetiapine fumarate (Seroquel) is the most recently introduced atypical antipsychotic and is indicated for the management of the manifestations of psychotic disorders and schizophrenia. Quetiapine, like clozapine (the archetypal atypical antipsychotic), interacts with a broad range of neurotransmitter receptors and has a higher affinity for serotonin (5-HT(2A)) receptors relative to dopamine (D(2)) receptors in the brain. Further, quetiapine's pharmacological effects appear selective for the mesolimbic and mesocortical dopamine systems, which are believed to be the areas of the brain responsible for the therapeutic effects of antipsychotics. In contrast to most standard antipsychotics and some atypical antipsychotics, quetiapine's effects on the nigrostriatal dopamine system, which is responsible for the extrapyramidal (or motor) side effects, are minimal. Quetiapine also has minimal activity on dopamine receptors in the tuberoinfundibular dopamine system, thereby avoiding the problem of hyperprolactinemia, common with the standard antipsychotics and some atypical antipsychotics. Because of these properties, quetiapine is an effective antipsychotic agent with a relatively benign side effect profile. Several large, placebo- and active-controlled, multicenter trials have shown quetiapine to be effective against both positive (e.g., hallucinations, delusions) and negative symptoms (e.g., emotional withdrawal, apathy) and to have benefits in reducing hostility, aggression and affective symptoms. Patients on long-term treatment report high compliance, good satisfaction, increased ability to function and improvements consistent with a better quality of life. Because of quetiapine's excellent tolerability profile, its use is particularly appropriate in patients especially sensitive to adverse effects, e.g., elderly patients with psychotic symptoms and other neurological disorders such as Parkinson's and Alzheimer's disease.
过去10年中抗精神病药物研发工作的目标是开发出疗效更高、安全性更好且副作用比传统抗精神病药物更少的药物。这些新型药物,通常被称为非典型抗精神病药物,对治疗精神分裂症的阳性和阴性症状均有效,而且与传统药物相比,其神经和内分泌相关的副作用更少。因此,患者更有可能长期接受治疗,从而预防复发和减少昂贵的住院治疗。富马酸喹硫平(思瑞康)是最近推出的非典型抗精神病药物,用于治疗精神障碍和精神分裂症的症状。喹硫平与氯氮平(典型的非典型抗精神病药物)一样,能与多种神经递质受体相互作用,并且相对于大脑中的多巴胺(D(2))受体,它对5-羟色胺(5-HT(2A))受体具有更高的亲和力。此外,喹硫平的药理作用似乎对中脑边缘和中脑皮质多巴胺系统具有选择性,据信这两个区域是大脑中对抗精神病药物治疗效果起作用的区域。与大多数标准抗精神病药物和一些非典型抗精神病药物不同,喹硫平对负责锥体外系(或运动)副作用的黑质纹状体多巴胺系统的作用极小。喹硫平对结节漏斗多巴胺系统中的多巴胺受体活性也极小,从而避免了标准抗精神病药物和一些非典型抗精神病药物常见的高催乳素血症问题。由于这些特性,喹硫平是一种有效的抗精神病药物,其副作用相对较小。多项大规模、安慰剂对照和活性药物对照的多中心试验表明,喹硫平对阳性症状(如幻觉、妄想)和阴性症状(如情感退缩、冷漠)均有效,并且在减少敌意、攻击性和情感症状方面有疗效。长期治疗的患者报告依从性高、满意度好、功能能力增强以及生活质量改善。由于喹硫平具有出色的耐受性,它特别适用于对不良反应特别敏感的患者,例如患有精神症状的老年患者以及患有帕金森病和阿尔茨海默病等其他神经疾病的患者。