Background

In spite of the substantial therapeutic efficacy of triptans, their site of action is still debated. Subcutaneous sumatriptan is the most efficacious symptomatic treatment for cluster headache (CH) patients, showing therapeutic onset within a few minutes after injection even in migraine patients. However, whether subcutaneous sumatriptan is able to reach the CNS within this short time frame is currently unknown.

Methods

Here, by means of liquid chromatography/mass spectrometry, we investigated peripheral and brain distribution of subcutaneous sumatriptan soon after injection in rats at a dose equivalent to that used in patients. Tissue sumatriptan contents were compared to those of oxazepam, a prototypical lipophilic, neuroactive drug.

Results

We report that sumatriptan accumulated within brain regions of relevance to migraine and CH pathogenesis such as the hypothalamus and the brainstem as soon as 1 and 5 minutes after injection. Notably, sumatriptan brain distribution was faster than that of oxazepam, reaching concentrations exceeding its reported binding affinity for 5HT1_B/D receptors, and in the range of those able to inhibit neurotransmitter release in vivo.

Conclusion

Our findings indicate that sumatriptan distributes within the CNS soon after injection, and are in line with prompt pain relief by parenteral sumatriptan in CH patients.

中文翻译：

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大鼠皮下舒马曲坦的超快速脑摄取：对丛集性头痛治疗的意义。

背景

尽管曲普坦具有显着的治疗功效，但其作用部位仍存在争议。皮下舒马曲坦对丛集性头痛（CH）患者是最有效的对症治疗，即使在偏头痛患者中，注射后几分钟内也显示出治疗发作。然而，目前尚不清楚皮下舒马曲坦是否能够在此短时间内到达中枢神经系统。

方法

在这里，我们通过液相色谱/质谱法研究了大鼠皮下注射舒马曲坦后的外周和大脑分布，其剂量与患者使用的剂量相当。将舒马曲坦的组织含量与奥沙西m（一种典型的亲脂神经活性药物）的含量进行了比较。

结果

我们报告说，舒马曲坦在注射后1和5分钟内会在与偏头痛和CH发病机制（例如下丘脑和脑干）相关的大脑区域内积累。值得注意的是，舒马曲坦的脑部分布比奥沙西m快，达到的浓度超过了其报告的对5HT1 _{B / D}受体的结合亲和力，并且超出了能够抑制体内神经递质释放的范围。

结论

我们的研究结果表明，舒马曲坦注射后不久就分布在中枢神经系统内，与肠外舒马曲坦在CH患者中迅速缓解疼痛相符。