Neuropharmacological Profile of an Atypical Antipsychotic, NRA0562

Shiho Hirota, Naoya Kawashima, Shigeyuki Chaki, Shigeru Okuyama
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引用次数: 4

Abstract

Schizophrenia is a serious and disabling psychiatric disorder affecting approximately 1% of the world's population. Anew generation of atypical antipsychotics has been introduced over the past decade. These atypical antipsychotics have comparable or greater efficacy than traditional antipsychotics in the treatment of the psychotic symptoms of schizophrenia and a much improved neurologic side effect profile. This paper reviews the pharmacological efficacy and safety of a potential atypical antipsychotic, NRA0562.

NRA0562 has a high affinity for dopamine D1, D2L, D4.2, 5-HT2A receptors as well as α1-adrenoceptors, and has a moderate affinity for H1 receptors. NRA0562 strongly binds to 5-HT2A receptors and α1-adrenoceptors in the frontal cortex, its binding to striatal D2 receptors is weaker, similar to that of clozapine.

NRA562 displayed potent antipsychotic activities in animal models of schizophrenia, such as methamphetamine (MAP)-induced hyperactivity, apomorphine-induced disruption of pre-pulse inhibition and conditioned avoidance test. NRA0562 is more potent in reversing the inhibitory effects of MAP at A10 than at A9 dopamine neurons. It increased Fos-like immunoreactivity in the nucleus accumbens more effectively than in the dorsolateral striatum, indicating that NRA0562 has the profile of an atypical antipsychotic. In vivo assays for extrapyramidal side effect liability showed that NRA0562 has a low rate of neurological side effects. Thus, NRA0562 may have unique antipsychotic activity with a lower propensity for extrapyramidal side effects.

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一种非典型抗精神病药的神经药理学特征,NRA0562
精神分裂症是一种严重的致残性精神疾病,影响着大约1%的世界人口。新一代非典型抗精神病药物在过去十年中被引入。这些非典型抗精神病药物在治疗精神分裂症的精神病症状方面具有与传统抗精神病药物相当或更高的疗效,并且大大改善了神经系统副作用。本文综述了一种潜在的非典型抗精神病药NRA0562的药理疗效和安全性。NRA0562对多巴胺D1、D2L、D4.2、5-HT2A受体和α1-肾上腺素受体具有高亲和力,对H1受体具有中等亲和力。NRA0562与额叶皮层5-HT2A受体和α - 1肾上腺素受体结合较强,与纹状体D2受体结合较弱,与氯氮平相似。NRA562在精神分裂症动物模型中表现出较强的抗精神病活性,如甲基苯丙胺(MAP)诱导的多动、阿帕吗啡诱导的脉冲前抑制中断和条件回避试验。与A9多巴胺神经元相比,NRA0562在逆转MAP在A10的抑制作用方面更有效。它比背外侧纹状体更有效地增加伏隔核的fos样免疫反应性,表明NRA0562具有非典型抗精神病药物的特征。体内锥体外系副作用倾向试验表明,NRA0562具有较低的神经系统副作用率。因此,NRA0562可能具有独特的抗精神病活性,并具有较低的锥体外系副作用倾向。
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