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拉米地坦用于治疗偏头痛。

Lasmiditan for the treatment of migraine.

作者信息

Capi Matilde, de Andrés Fernando, Lionetto Luana, Gentile Giovanna, Cipolla Fabiola, Negro Andrea, Borro Marina, Martelletti Paolo, Curto Martina

机构信息

a Experimental Immunology Laboratory , Fondazione Luigi Maria Monti, IDI-IRCCS , Rome , Italy.

b CICAB Clinical Research Centre , Extremadura University Hospital and Medical School , Badajoz , Spain.

出版信息

Expert Opin Investig Drugs. 2017 Feb;26(2):227-234. doi: 10.1080/13543784.2017.1280457.

Abstract

Migraine is one of the most common diseases in the world, with high economical and subjective burden. Migraine acute therapy is nowadays based on specific and non-specific drugs but up to 40% of episodic migraineurs still have unmet treatment needs and over 35% do not benefit from triptans administration. Serotonin-1F receptors have been identified in trigeminal system and became an ideal target for anti-migraine drug development as potential trigeminal neural inhibitors. Lasmiditan, a novel serotonin1F receptor agonist, showed specific affinity in vitro for the receptor without any vasoconstrictive action and inhibited markers associated with electrical stimulation of trigeminal ganglion in migraine animal models. Areas covered: This article reviews both preclinical and clinical studies on lasmiditan as a potential acute therapy for migraine, as well as pharmacokinetic and pharmacodynamic features. It also summarizes safety and tolerability data gathered in the various human studies. Expert opinion: The absence of vasoconstrictive effects makes lasmiditan a promising novel migraine acute therapy. Although preclinical and Phase I and II studies established a significant efficacy, the limited knowledge about pharmacokinetics and metabolism, the high rate of non-serious central nervous system side effects and the lack of larger studies remain still a matter of concern that should be addressed in future studies.

摘要

偏头痛是世界上最常见的疾病之一,具有高昂的经济负担和主观负担。目前偏头痛的急性治疗基于特异性和非特异性药物,但高达40%的发作性偏头痛患者仍有未满足的治疗需求,超过35%的患者未从曲坦类药物治疗中获益。5-羟色胺-1F受体已在三叉神经系统中被发现,并作为潜在的三叉神经抑制剂成为抗偏头痛药物研发的理想靶点。拉米地坦是一种新型5-羟色胺1F受体激动剂,在体外对该受体表现出特异性亲和力,且无任何血管收缩作用,并在偏头痛动物模型中抑制了与三叉神经节电刺激相关的标志物。涵盖领域:本文综述了拉米地坦作为偏头痛潜在急性治疗药物的临床前和临床研究,以及其药代动力学和药效学特征。还总结了在各种人体研究中收集的安全性和耐受性数据。专家观点:拉米地坦没有血管收缩作用,使其成为一种有前景的新型偏头痛急性治疗药物。尽管临床前研究以及I期和II期研究证实了其显著疗效,但对其药代动力学和代谢的了解有限、非严重中枢神经系统副作用发生率较高以及缺乏更大规模的研究,这些仍是未来研究中需要解决的令人担忧的问题。

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