Belyaeva Irina I, Subbotina Anna G, Eremenko Ivan I, Tarasov Vadim V, Chubarev Vladimir N, Schiöth Helgi B, Mwinyi Jessica
Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala, Uppsala, Sweden.
Department of Pharmacology, Institute of Pharmacy, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.
Front Pharmacol. 2022 Feb 10;12:820214. doi: 10.3389/fphar.2021.820214. eCollection 2021.
Primary headache disorders, such as migraine, tension-type headache (TTH), and cluster headache, belong to the most common neurological disorders affecting a high percentage of people worldwide. Headache induces a high burden for the affected individuals on the personal level, with a strong impact on life quality, daily life management, and causes immense costs for the healthcare systems. Although a relatively broad spectrum of different pharmacological classes for the treatment of headache disorders are available, treatment effectiveness is often limited by high variances in therapy responses. Genetic variants can influence the individual treatment success by influencing pharmacokinetics or pharmacodynamics of the therapeutic as investigated in the research field of pharmacogenetics. This review summarizes the current knowledge on important primary headache disorders, including migraine, TTH, and cluster headache. We also summarize current acute and preventive treatment options for the three headache disorders based on drug classes and compounds taking important therapy guidelines into consideration. Importantly, the work summarizes and discusses the role of genetic polymorphisms regarding their impact on metabolism safety and the effect of therapeutics that are used to treat migraine, cluster headache, and TTH exploring drug classes such as nonsteroidal anti-inflammatory drugs, triptans, antidepressants, anticonvulsants, calcium channel blockers, drugs with effect on the renin-angiotensin system, and novel headache therapeutics such as ditans, anti-calcitonin-gene-related peptide antibodies, and gepants. Genetic variants in important phase I-, II-, and III-associated genes such as cytochrome P450 genes, UGT genes, and different transporter genes are scrutinized as well as variants in genes important for pharmacodynamics and several functions outside the pharmacokinetic and pharmacodynamic spectrum. Finally, the article evaluates the potential and limitations of pharmacogenetic approaches for individual therapy adjustments in headache disorders.
原发性头痛疾病，如偏头痛、紧张型头痛（TTH）和丛集性头痛，属于全球影响很大一部分人群的最常见神经系统疾病。头痛在个人层面给患者带来了沉重负担，对生活质量、日常生活管理产生强烈影响，并给医疗系统造成巨大成本。尽管有相对广泛的不同药理类别可用于治疗头痛疾病，但治疗效果往往受到治疗反应高度差异的限制。基因变异可通过影响治疗药物的药代动力学或药效学来影响个体治疗的成功，这在药物遗传学研究领域已得到研究。本综述总结了关于重要原发性头痛疾病的现有知识，包括偏头痛、TTH和丛集性头痛。我们还根据药物类别和化合物，同时考虑重要的治疗指南，总结了这三种头痛疾病目前的急性和预防性治疗选择。重要的是，这项工作总结并讨论了基因多态性在代谢安全性方面的作用，以及用于治疗偏头痛、丛集性头痛和TTH的治疗药物的效果，探讨了非甾体抗炎药、曲坦类药物、抗抑郁药、抗惊厥药、钙通道阻滞剂、对肾素 - 血管紧张素系统有作用的药物，以及新型头痛治疗药物如双氢麦角胺、抗降钙素基因相关肽抗体和 gepants等药物类别。对重要的I期、II期和III期相关基因中的基因变异，如细胞色素P450基因、UGT基因和不同转运蛋白基因进行了仔细研究，以及对药效学重要的基因和药代动力学和药效学范围之外的几种功能的基因变异也进行了研究。最后，本文评估了药物遗传学方法在头痛疾病个体化治疗调整中的潜力和局限性。
