Abstract：
Patients with epilepsy require improved medications. Purinergic receptors were identified as late as 1976 and are slowly emerging as potential drug targets for the discovery of antiseizure medications. While compounds interacting with these receptors have been approved for use as medicines (e.g., gefapixant for cough) and continue to be explored for a number of diseases (e.g., pain, cancer), there have been no purinergic receptor antagonists that have been advanced for epilepsy. There are very few studies on the channel conducting receptors, P2X3 and P2X4, that suggest their possible role in seizure generation or control. However, the limited data available provides some compelling reasons to believe that they could be valuable antiseizure medication drug targets. The data implicating P2X3 and P2X4 receptors in epilepsy includes the role played by ATP in neuronal excitability and seizures, receptor localization, increased receptor expression in epileptic brain, the involvement of these receptors in seizure-associated inflammation, crosstalk between these purinergic receptors and neuronal processes involved in seizures (GABAergic and glutamatergic neurotransmission), and the significant attenuation of seizures and seizure-like activity with P2X receptor blockade. The discovery of new and selective antagonists for P2X3 and P2X4 receptors is ongoing, armed with new structural data to guide rational design. The availability of safe, brain-penetrant compounds will likely encourage the clinical exploration of epilepsy as a disease entity.
摘要：
癫痫患者需要改进药物治疗。直到1976年才发现嘌呤能受体，并逐渐成为发现抗癫痫药物的潜在药物靶标。虽然与这些受体相互作用的化合物已被批准用作药物(例如，gefapixant用于咳嗽)，并继续探索用于多种疾病(例如，疼痛,cancer),目前还没有嘌呤能受体拮抗剂治疗癫痫。关于通道传导受体的研究很少，P2X3和P2X4，这表明它们在癫痫发作产生或控制中的可能作用。然而,现有的有限数据提供了一些令人信服的理由来相信它们可能是有价值的抗癫痫药物靶标.癫痫中涉及P2X3和P2X4受体的数据包括ATP在神经元兴奋性和癫痫发作中所起的作用，受体定位，癫痫脑中受体表达增加，这些受体参与癫痫相关的炎症，这些嘌呤能受体和参与癫痫发作的神经元过程之间的串扰（GABA能和谷氨酸能神经传递），以及P2X受体阻断对癫痫发作和癫痫样活动的显着减弱。新的和选择性的P2X3和P2X4受体拮抗剂的发现正在进行中，配备新的结构数据来指导合理的设计。安全的可用性，脑渗透性化合物可能会鼓励癫痫作为一种疾病实体的临床探索。
