Dusitanond Petcharat, Young William B
Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, USA.
Cent Nerv Syst Agents Med Chem. 2009 Mar;9(1):63-70. doi: 10.2174/187152409787601888.
Many dopamine antagonists are proven acute migraine treatments. Genetic studies also imply that polymorphisms in dopamine genes (DRD2 receptors) in persons with migraine may create dopamine hypersensitivity. However, treatment is limited by the adverse event profiles of conventional neuroleptics including extrapyramidal symptoms, anticholinergic and antihistaminergic effects, hyperprolactinemia, and prolonged cardiac QT interval. Atypical neuroleptics cause less extrapyramial symptoms and some atypical neuroleptics, including olanzapine and quetiapine, may be beneficial as both acute and preventive migraine treatment. The combination of prochlorperazine, indomethacin, and caffeine is effective in the treatment of the acute migraine attack. The mechanism of action by which neuroleptics relieve headache is probably related to dopamine D2 receptor antagonist. Other actions via serotonin (5HT) receptor antagonists may also be important, particularly for migraine prevention. Additional studies to clarify the mechanism of action of neuroleptics in migraine could lead to new drugs and better management of migraine.
许多多巴胺拮抗剂已被证实可有效治疗急性偏头痛。基因研究还表明,偏头痛患者多巴胺基因(DRD2受体)的多态性可能导致多巴胺超敏反应。然而,传统抗精神病药物的不良事件,包括锥体外系症状、抗胆碱能和抗组胺作用、高泌乳素血症以及心脏QT间期延长,限制了其治疗应用。非典型抗精神病药物引起的锥体外系症状较少,一些非典型抗精神病药物,包括奥氮平和喹硫平,可能对急性和预防性偏头痛治疗均有益。氯丙嗪、吲哚美辛和咖啡因的组合对治疗急性偏头痛发作有效。抗精神病药物缓解头痛的作用机制可能与多巴胺D2受体拮抗剂有关。通过5-羟色胺(5HT)受体拮抗剂的其他作用可能也很重要,特别是对于偏头痛的预防。进一步研究以阐明抗精神病药物在偏头痛中的作用机制,可能会带来新的药物和更好的偏头痛治疗方法。