Department of Biochemistry, Matsumoto Dental University, Shioziri 399-0781, Japan; Department of Membrane Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-0082, Japan.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan.
Trends Pharmacol Sci. 2018 Jan;39(1):13-23. doi: 10.1016/j.tips.2017.10.007. Epub 2017 Nov 13.
Clodronate is a first-generation bisphosphonate used worldwide for antiresorptive therapy for osteoporosis. Although clodronate is analgesic in nature, its mechanism and efficacy were unknown for some time. Recently, clodronate was identified as a selective and potent inhibitor for vesicular nucleotide transporter (VNUT), a transporter responsible for vesicular storage of ATP. Clodronate inhibits vesicular ATP release from neurons and reduces chronic neuropathic and inflammatory pain following blockade of purinergic chemical transmission. Its effectiveness is stronger, faster acting, and longer lasting than that of existing drugs such as pregabalin. Thus, clodronate might be a promising drug for attenuating chronic neuropathic pain and opens a new field of drug discovery as a presynaptic blocker for purinergic chemical transmission.
氯膦酸二钠是第一代双膦酸盐，被广泛用于抗骨质疏松症的抗吸收治疗。尽管氯膦酸二钠具有镇痛作用，但它的作用机制和疗效在一段时间内并不清楚。最近，氯膦酸二钠被鉴定为囊泡核苷酸转运体（VNUT）的选择性和有效抑制剂，VNUT 是负责 ATP 囊泡储存的转运体。氯膦酸二钠抑制神经元中囊泡 ATP 的释放，并阻断嘌呤能化学传递后减轻慢性神经病理性和炎性疼痛。其有效性比现有药物如普瑞巴林更强、起效更快、持续时间更长。因此，氯膦酸二钠可能是一种有前途的药物，可用于减轻慢性神经病理性疼痛，并开辟了作为嘌呤能化学传递的突触前阻滞剂的药物发现新领域。
