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首页> 外文期刊>Drugs of today: Medicamentos de actualidad >Dextromethorphan/quinidine sulfate for pseudobulbar affect.
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Dextromethorphan/quinidine sulfate for pseudobulbar affect.

机译：硫酸右美沙芬/硫酸奎尼丁对假球的影响。

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摘要

A new agent containing a combination of dextromethorphan (DM) and quinidine (Q) is currently under development for the treatment of pseudobulbar affect (PBA). PBA is a disorder of emotional regulation, characterized by uncontrollable outbursts of laughing and/or crying that are disproportionate to the emotions being experienced. The pathophysiology of PBA is currently unknown, although the disorder is thought to occur exclusively in the setting of neurological disease. The most influential theory on PBA posits that emotional outbursts are being generated autonomously in the brain stem due to loss of regulatory control by the frontal lobe. Although rarely life-threatening, PBA can have significant impact on patient quality of life, and thus merits treatment. There are currently no approved treatments for PBA. Several agents have been found to be effective in small placebo-controlled trials and case series, with the most commonly used agents being tricyclic antidepressants and selective serotonin reuptake inhibitors. Both these treatments are inexpensive and relatively low-risk, although the quality and quantity of data available on their efficacy are not optimal. DM has several pharmacological mechanisms of action relevant to the brain. It is an N-methyl-D-aspartate (NMDA) receptor antagonist, which prompted investigators to study its potential for slowing progression in amyotrophic lateral sclerosis (ALS), where glutamate toxicity is thought to be a factor. The combination agent DM/Q was developed to slow the metabolism of DM by P450 2D6 enzymes in the liver. DM/Q was not effective in slowing ALS progression, but patients noted that it helped to control their emotional outbursts, suggesting it might be useful as a treatment for PBA. DM is also a sigma-1 receptor agonist. These receptors are widely distributed in the brain, but probably most heavily in the limbic system, suggesting that DM may exert its emotion-controlling effects via these receptors. The endogenous ligands for sigma-1 receptors are not altogether known, although they appear to include gonadal steroids. DM/Q was recently shown to be effective in reducing the severity of PBA in two large studies of ALS and multiple sclerosis, which are probably the most common neurological settings. These are the largest treatment studies of PBA ever done. The agent was safe and relatively well tolerated. Further studies are being conducted to see if efficacy can be maintained with lower doses of quinidine. If DM/Q is approved by the U.S. Food and Drug Administration for treatment of PBA, it would be the first agent approved for this purpose. Currently, the antidepressants are probably the most attractive pharmacologic options for treatment of PBA. The choice of whether to use DM/Q in this setting will likely depend on individual patient factors as well as cost.
机译：目前正在开发一种包含右美沙芬（DM）和奎尼丁（Q）的组合的新型药物，用于治疗假球情感（PBA）。 PBA是一种情绪调节障碍，其特征在于无法控制的笑声和/或哭声爆发与所经历的情绪不成比例。 PBA的病理生理学目前未知，尽管据认为该疾病仅在神经系统疾病中发生。关于PBA的最具影响力的理论认为，由于额叶失去对调节的控制，情绪爆发在脑干中自动产生。尽管很少危及生命，但PBA可能会对患者的生活质量产生重大影响，因此值得进行治疗。当前没有批准的PBA治疗方法。在小型安慰剂对照试验和病例系列中，发现有几种药物有效，最常用的药物是三环抗抑郁药和选择性5-羟色胺再摄取抑制剂。尽管可获得的关于疗效的数据的质量和数量都不是最佳的，但这两种治疗方法均价格便宜且风险相对较低。 DM具有与大脑有关的几种药理作用机理。它是一种N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，促使研究人员研究了其在肌萎缩性侧索硬化症（ALS）中延缓其进展的潜力，其中谷氨酸毒性被认为是一个因素。开发了DM / Q组合剂以减缓肝脏中P450 2D6酶对DM的代谢。 DM / Q不能有效减慢ALS的进展，但患者注意到它有助于控制情绪爆发，表明它可能作为PBA的治疗方法。 DM也是sigma-1受体激动剂。这些受体广泛分布在大脑中，但可能在边缘系统中分布最广，表明DM可能通过这些受体发挥其情绪控制作用。尽管sigma-1受体的内源性配体似乎包含性腺类固醇，但尚不完全了解。最近在两项大型的ALS和多发性硬化症研究（可能是最常见的神经系统疾病）中，DM / Q可有效降低PBA的严重程度。这些是有史以来最大的PBA治疗研究。该药物是安全的，耐受性相对较好。正在进行进一步的研究，以观察使用较低剂量的奎尼丁能否维持疗效。如果DM / Q被美国食品药品监督管理局批准用于PBA的治疗，它将是第一个为此目的批准的药物。目前，抗抑郁药可能是治疗PBA的最有吸引力的药理学选择。在这种情况下是否使用DM / Q的选择可能取决于各个患者因素以及成本。

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