Wheeler Glen
Curr Opin Investig Drugs. 2002 Mar;3(3):470-7.
Gabapentin has been approved for the treatment of neuropathic pain in six European countries, New Zealand and Australia, and numerous countries in Latin America. By January 2001, Pfizer was preparing to file an NDA in the US for this indication; by October 2001, this NDA had been filed with the FDA. The drug is a GABA analog, but is not a GABA mimetic, although some neurons that respond to gabapentin are GABAergic. Gabapentin, at relevant concentrations, binds to an auxiliary protein of voltage-gated calcium channels (a2/3) and apparently, as a result, modulates the action of calcium channels and neurotransmitter release. This may account for many of its pharmacological actions. Gabapentin is also a substrate for the large neutral amino acid transporter, and this may be the major route allowing gabapentin access to the CNS. Modulation of synaptic transmission between primary afferents and substantia gelatinosa neurons, and blockade of signal transduction, are two potential mechanisms of action, in addition to inhibition of glutamate release by voltage-sensitive calcium channels. In September 2001, Morgan Stanley predicted sales of US $1871 million in 2002 falling to US $413 million in 2006.
加巴喷丁已在六个欧洲国家、新西兰、澳大利亚以及许多拉丁美洲国家获批用于治疗神经性疼痛。到2001年1月，辉瑞公司正准备在美国就该适应症提交新药申请；到2001年10月，该新药申请已提交给美国食品药品监督管理局（FDA）。该药物是一种γ-氨基丁酸（GABA）类似物，但不是GABA模拟物，尽管一些对加巴喷丁有反应的神经元是GABA能神经元。在相关浓度下，加巴喷丁与电压门控钙通道的一种辅助蛋白（α2/δ）结合，显然，其结果是调节钙通道的作用和神经递质的释放。这可能解释了它的许多药理作用。加巴喷丁也是大中性氨基酸转运体的底物，这可能是加巴喷丁进入中枢神经系统的主要途径。除了通过电压敏感性钙通道抑制谷氨酸释放外，调节初级传入神经元与脊髓背角胶状质神经元之间的突触传递以及阻断信号转导是另外两种潜在的作用机制。2001年9月，摩根士丹利预测其2002年销售额为18.71亿美元，到2006年将降至4.13亿美元。
