Cheng Jen-Kun, Chiou Lih-Chu
Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei.
J Pharmacol Sci. 2006;100(5):471-86. doi: 10.1254/jphs.cr0050020. Epub 2006 Feb 11.
Gabapentin, a gamma-aminobutyric acid (GABA) analogue anticonvulsant, is also an effective analgesic agent in neuropathic and inflammatory, but not acute, pain systemically and intrathecally. Other clinical indications such as anxiety, bipolar disorder, and hot flashes have also been proposed. Since gabapentin was developed, several hypotheses had been proposed for its action mechanisms. They include selectively activating the heterodimeric GABA(B) receptors consisting of GABA(B1a) and GABA(B2) subunits, selectively enhancing the NMDA current at GABAergic interneurons, or blocking AMPA-receptor-mediated transmission in the spinal cord, binding to the L-alpha-amino acid transporter, activating ATP-sensitive K(+) channels, activating hyperpolarization-activated cation channels, and modulating Ca(2+) current by selectively binding to the specific binding site of [(3)H]gabapentin, the alpha(2)delta subunit of voltage-dependent Ca(2+) channels. Different mechanisms might be involved in different therapeutic actions of gabapentin. In this review, we summarized the recent progress in the findings proposed for the antinociceptive action mechanisms of gabapentin and suggest that the alpha(2)delta subunit of spinal N-type Ca(2+) channels is very likely the analgesic action target of gabapentin.
加巴喷丁是一种γ-氨基丁酸（GABA）类似物抗惊厥药，在治疗神经性疼痛和炎性疼痛而非急性疼痛方面，无论是全身用药还是鞘内给药，它都是一种有效的镇痛药。此外，它还被提议用于治疗焦虑症、双相情感障碍和潮热等其他临床适应症。自加巴喷丁研发以来，人们针对其作用机制提出了多种假说。这些假说包括选择性激活由GABA(B1a)和GABA(B2)亚基组成的异二聚体GABA(B)受体、选择性增强GABA能中间神经元的NMDA电流、或阻断脊髓中AMPA受体介导的传递、与L-α-氨基酸转运体结合、激活ATP敏感性钾通道、激活超极化激活阳离子通道，以及通过选择性结合[³H]加巴喷丁的特异性结合位点（电压依赖性钙通道的α₂δ亚基）来调节钙电流。加巴喷丁的不同治疗作用可能涉及不同的机制。在这篇综述中，我们总结了加巴喷丁抗伤害感受作用机制研究的最新进展，并提出脊髓N型钙通道的α₂δ亚基很可能是加巴喷丁的镇痛作用靶点。
