摘要
苦参碱类生物碱(包括有苦参碱、氧化苦参碱、氧化槐定碱、槐果碱、氧化槐果碱等)具有镇痛作用,镇痛特征是以中枢性为主、无成瘾性和耐药性,综述其镇痛作用及作用机制研究进展。苦参碱类生物碱的中枢性镇痛作用机制可能是:激活大麻素受体-2和上调电压门控钙离子N-型通道表达,促进抑制性神经递质(γ-氨基丁酸、甘氨酸)合成和释放,下调GAT-1表达,使突触间隙γ-氨基丁酸浓度升高以及上调γ-氨基丁酸-A受体表达,从而增强γ-氨基丁酸能神经功能。γ-氨基丁酸能神经功能的增强可抑制兴奋性神经递质谷氨酸过度表达并下调NMDA受体和蛋白激酶Cγ表达,降低NMDA受体对谷氨酸的兴奋性,从而下调电压门控钙离子L-型通道的表达,抑制钙离子内流,阻滞CaMKⅡ/CREB通路,减轻炎症反应和产生镇痛作用。
Matrine-type alkaloids including matrine, oxymatrine, oxysophoridine, sophocarpine, and oxysophocarpine, which have antinociceptive effects with the characteristics of central, no addiction, and no drug-tolerance. This review summarizes the research progress of antinociceptive effects and related mechanisms of matrine-type alkaloids. Central antinociceptive mechanism of matrine-type alkaloids may be to activate cannabine receptor-2, up-regulate the expression of N-type voltage-gated calcium channels, improve the synthesis and release of inhibitory neurotransmitters, γ-aminobutyric acid（GABA） and glycine, down-regulate the expression of GABA transporter 1（GAT-1）, increase the concentration of GABA in synaptic cleft, and up-regulate the expression of GABA receptor, thus strengthening GABAergic nerve function. Enhancement of GABAergic nerve function can inhibit the over expression of excitatory neurotransmitter glutamic acid, and down-regulate the expression of N-methyl-D-aspartate（NMDA） receptor, and protein kinase Cγ to decrease the excitation of NMDA receptor response to glutamate, thus down-regulating the expression of L-type voltage-gated calcium channels, inhibiting Ca2＋ influent, and blocking CaMKⅡ/CREB pathway to inhibit inflammation and produce analgesic action.
作者
张明发
沈雅琴
ZHANG Mingfa;SHEN Yaqin(Shanghai Meiyou Pharmaceutical Co. Ltd., Shanghai 201204, China)
出处
《药物评价研究》
CAS
2018年第5期904-911,共8页
Drug Evaluation Research
