The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog.
The effects of trazodone with L-tryptophan on sleep-disordered breathing in the English bulldog.
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DOI：
10.1164/ajrccm.160.5.9812007
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发表时间：
1999-11
影响因子：
24.7
通讯作者：
S. Veasey;P. Fenik;K. Panckeri;A. Pack;J. Hendricks
中科院分区：
文献类型：
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作者：
S. Veasey;P. Fenik;K. Panckeri;A. Pack;J. Hendricks
阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是一种常见的疾病，目前尚无普遍有效的药物治疗。我们假设在OSAHS中，兴奋性肾上腺素能的影响对于维持清醒时上气道的通畅是重要的，而在睡眠中，肾上腺素能驱动的减少在上气道塌陷和OSAHS中起着重要作用。先前报告的OSAHS患者对阿托伐他汀的小反应可能部分与研究设计和所选药物/剂量有关。因此，我们进行了多项试验/剂量、多剂量、随机睡眠研究，在我们的OSAHS动物模型（英国斗牛犬）中测试了阿托伐他汀能药物、曲唑酮和L-色氨酸组合的有效性。曲唑酮/L-色氨酸导致非快速眼动睡眠（NREMS）和快速眼动睡眠（REMS）中呼吸事件的剂量依赖性减少。在NREMS期间，呼吸紊乱指数（RDI）+/-标准误为6.3 +/- 1.4次事件/h（安慰剂）和0.9 +/- 0.3（最高剂量），p < 0.01。在REMS期间，RDI为31.4 +/- 6.1起事件/h（安慰剂）和11.5 +/- 4.3（最高剂量），p = 0.002。曲唑酮/L-色氨酸剂量依赖性地减少睡眠碎片，p = 0.03，增加睡眠效率，p = 0.005，增强慢波睡眠，p = 0.0004，并最大限度地减少睡眠相关的上呼吸道扩张活性抑制，p < 0.02。曲唑酮与L-色氨酸可以治疗OSAHS动物模型中的睡眠呼吸障碍（SDB）;这种治疗的有效性可能与睡眠中上气道扩张剂活性增加和/或慢波睡眠增强有关。
Obstructive sleep apnea hypopnea syndrome (OSAHS) is a prevalent disorder, for which there are no universally effective pharmacotherapeutics. We hypothesized that in OSAHS, excitatory serotoninergic influences are important for maintaining patency of the upper airway in waking, and that in sleep, reduced serotoninergic drive plays a significant role in upper airway collapse and OSAHS. The previously reported small responses in humans with OSAHS to serotoninergics may relate, in part, to study design and the drugs/doses selected. We therefore performed multitrials/dose, multidose, randomized sleep studies testing the effectiveness of a combination of serotoninergics, trazodone, and L-tryptophan, in our animal model of OSAHS, the English bulldog. Trazodone/L-tryptophan caused dose-dependent reductions in respiratory events in non-rapid-eye-movement sleep (NREMS) and rapid-eye-movement sleep (REMS). During NREMS, the respiratory disturbance index (RDI) +/- standard error was 6.3 +/- 1.4 events/h (placebo) and 0.9 +/- 0.3 (highest dose), p < 0.01. During REMS, the RDI was 31.4 +/- 6.1 events/h (placebo) and 11.5 +/- 4.3 (highest dose), p = 0.002. Trazodone/ L-tryptophan dose-dependently reduced sleep fragmentation, p = 0.03, increased sleep efficiency, p = 0.005, enhanced slow-wave sleep, p = 0.0004, and minimized sleep-related suppression of upper airway dilator activity, p < 0.02. Trazodone with L-tryptophan can treat sleep-disordered breathing (SDB) in an animal model of OSAHS; the effectiveness of this therapy may be related to increased upper airway dilator activity in sleep and/or enhanced slow-wave sleep.