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.

氯膦酸盐是第一代双膦酸盐，在世界范围内用于骨质疏松症的抗吸收治疗。尽管氯膦酸盐本质上是止痛药，但其机理和功效尚不清楚。最近，氯膦酸盐被鉴定为水泡核苷酸转运蛋白（VNUT）的选择性和有效抑制剂，VNUT是负责ATP的水泡贮存的转运蛋白。氯膦酸盐可抑制嘌呤能化学传递受阻，从而抑制神经元中囊泡ATP的释放，并减轻慢性神经病和炎症性疼痛。与普瑞巴林等现有药物相比，它的功效更强，作用更快，持续时间更长。因此，氯膦酸盐可能是减轻慢性神经性疼痛的一种有前途的药物，并为嘌呤能化学传递的突触前阻滞剂开辟了新的药物发现领域。