Dibas Jamileh, Al-Saad Houssam, Dibas Adnan
Faculty of Pharmacy, Applied University, Amman, Jordan.
North Texas Eye Research Institute, Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
Neural Regen Res. 2019 Mar;14(3):395-398. doi: 10.4103/1673-5374.245466.
Since the discovery of acid-sensing ion channels in 1997, their importance in the health of neurons and other non-neuronal cells has gained significant importance. Acid-sensing ion channels play important roles in mediating pain sensation during diseases such as stroke, inflammation, arthritis, cancer, and recently migraine. More interestingly, acid-sensing ion channels may explain the sex differences in pain between males and females. Also, the ability of acid-sensing ion channel blockers to exert neuroprotective effects in a number of neurodegenerative diseases has added a new dimension to their therapeutic value. The current failure rate of ~45% of new drugs (due to toxicity issues) and saving of up to 7 years in the life span of drug approval makes drug repurposing a high priority. If acid-sensing ion channels' blockers undergo what is known as "drug repurposing", there is a great potential to bring them as medications with known safety profiles to new patient populations. However, the route of administration remains a big challenge due to their poor penetration of the blood brain and retinal barriers. In this review, the promise of using acid-sensing ion channel blockers as neuroprotective drugs is discussed.
自1997年酸敏感离子通道被发现以来，它们在神经元和其他非神经元细胞健康中的重要性已变得极为重要。酸敏感离子通道在诸如中风、炎症、关节炎、癌症以及最近发现的偏头痛等疾病过程中介导痛觉方面发挥着重要作用。更有趣的是，酸敏感离子通道可能解释了男性和女性在疼痛方面的性别差异。此外，酸敏感离子通道阻滞剂在多种神经退行性疾病中发挥神经保护作用的能力为其治疗价值增添了新的维度。目前约45%的新药失败率（由于毒性问题）以及药物获批寿命最多可节省7年，使得药物重新利用成为当务之急。如果酸敏感离子通道阻滞剂进行所谓的“药物重新利用”，就有很大潜力将它们作为具有已知安全性的药物带给新的患者群体。然而，由于它们对血脑屏障和视网膜屏障的穿透性较差，给药途径仍然是一个巨大的挑战。在这篇综述中，将讨论使用酸敏感离子通道阻滞剂作为神经保护药物的前景。
