PDF(Pubmed)
Abstract：
Gabapentin (GBP) was originally developed as a potential agonist for Gamma-Amino-Butyric-Acid (GABA) receptors, aiming to inhibit the activation of pain-signaling neurons. Contrary to initial expectations, it does not bind to GABA receptors. Instead, it exhibits several distinct pharmacological activities, including: (1) binding to the alpha-2-delta protein subunit of voltage-gated calcium channels in the central nervous system, thereby blocking the excitatory influx of calcium; (2) reducing the expression and phosphorylation of CaMKII via modulation of ERK1/2 phosphorylation; (3) inhibiting glutamate release and interfering with the activation of NMDA receptors; (4) enhancing GABA synthesis; (5) increasing cell-surface expression of δGABA_A receptors, contributing to its antinociceptive, anticonvulsant, and anxiolytic-like effects. Additionally, GBP displays (6) inhibition of NF-kB activation and subsequent production of inflammatory cytokines, and (7) stimulation of the purinergic adenosine A1 receptor, which supports its anti-inflammatory and wound-healing properties. Initially approved for treating seizures and postherpetic neuralgia, GBP is now broadly used for various conditions, including psychiatric disorders, acute and chronic neuropathic pain, and sleep disturbances. Recently, as an eye drop formulation, it has also been explored as a therapeutic option for ocular surface discomfort in conditions such as dry eye, neurotrophic keratitis, corneal ulcers, and neuropathic ocular pain. This review aims to summarize the evidence supporting the molecular effects of GBP, with a special emphasis on its applications in ocular surface diseases.
摘要：
加巴喷丁（GBP）最初被开发为γ-氨基丁酸（GABA）受体的潜在激动剂，旨在抑制疼痛信号神经元的激活。与最初的期望相反，它不与GABA受体结合。相反，它表现出几种不同的药理活性，包括：（1）与中枢神经系统电压门控钙通道的α-2-δ蛋白亚基结合，从而阻断钙的兴奋性流入;(2)通过调节ERK1/2磷酸化降低CaMKII的表达和磷酸化;(3)抑制谷氨酸的释放并干扰NMDA受体的活化;(4)增强GABA的合成;(5)增加细胞表面δGABA_A受体的表达,有助于其抗伤害性，抗惊厥药,和抗焦虑作用.此外,GBP显示（6）抑制NF-kB激活和随后的炎性细胞因子的产生，和（7）刺激嘌呤能腺苷A1受体，支持其抗炎和伤口愈合特性。最初被批准用于治疗癫痫发作和带状疱疹后神经痛，英镑现在广泛用于各种条件，包括精神疾病,急性和慢性神经性疼痛，和睡眠障碍。最近,作为眼药水配方，它也被探索作为眼表不适的治疗选择，如干眼，神经营养性角膜炎，角膜溃疡,和神经性眼痛。这篇综述旨在总结支持GBP分子效应的证据，特别强调其在眼表疾病中的应用。
