Lovenberg T, Daly J W
Laboratory of Bioorganic Chemistry, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, Bethesda, MD 20892.
Neurochem Res. 1986 Nov;11(11):1609-21. doi: 10.1007/BF00965779.
A series of eight histrionicotoxins and two synthetic analogs inhibit binding of [3H]batrachotoxinin B to sites on voltage dependent sodium channels in brain membranes. Perhydrohistrionicotoxin (IC50 0.33 microM) and octahydrohistrionicotoxin (IC50 1.2 microM) are comparable in activities to potent local anesthetics. Histrionicotoxin (IC50 17 microM) and the other histrionicotoxins are much less potent. The histrionicotoxins also inhibit binding of [3H]phencyclidine to putative potassium channels in brain membranes. Histrionicotoxin (IC50 15 microM) and the other histrionicotoxins are much more potent than perhydrohistrionicotoxin (IC50 200 microM), but are at least 200-fold less potent than phencyclidine. The histrionicotoxins enhance binding of [3H]nitrendipine to sites on calcium channels in brain membranes, with the exception of perhydrohistrionicotoxin, which inhibits binding. Structure activity relationships at these channel sites and at the sites for noncompetitive blockers on the nicotinic acetylcholine receptor channel (AChR) complex differ. The histrionicotoxins are more potent at the sites on the AChR complex than at sites on other channels with the exception of perhydrohistrionicotoxin, which has comparable potency at the AChR complex and sodium channels.
一系列八种组氨酸毒素和两种合成类似物可抑制[3H]蟾毒素B与脑膜电压依赖性钠通道位点的结合。全氢组氨酸毒素（IC50为0.33微摩尔）和八氢组氨酸毒素（IC50为1.2微摩尔）的活性与强效局部麻醉剂相当。组氨酸毒素（IC50为17微摩尔）和其他组氨酸毒素的效力则低得多。组氨酸毒素还可抑制[3H]苯环利定与脑膜中假定钾通道的结合。组氨酸毒素（IC50为15微摩尔）和其他组氨酸毒素比全氢组氨酸毒素（IC50为200微摩尔）效力更强，但至少比苯环利定低200倍。除全氢组氨酸毒素抑制结合外，组氨酸毒素可增强[3H]尼群地平与脑膜中钙通道位点的结合。这些通道位点以及烟碱型乙酰胆碱受体通道（AChR）复合物上非竞争性阻滞剂位点的构效关系有所不同。除全氢组氨酸毒素在AChR复合物和钠通道上具有相当效力外，组氨酸毒素在AChR复合物位点比在其他通道位点更有效。
