PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产物提供了广泛的生物活性， 药物，其中许多药物具有独特的药理学特性， 活性和治疗潜力。 两百多种生物碱 已经在两栖动物皮肤的提取物中被鉴定出来。 这些 包括Batrachotoxins，其是钠有效活化剂 通道组织毒素它们是非竞争性的 烟碱受体通道复合物和钾通道，和 pumiliotoxins，其具有肌强直和强心活性， 对钠通道关闭的抑制作用。 矮油毒素B 作用于钠通道的特定部位， 通量和增强其他钠通道剂的作用，如 蝎毒素和短尾蝎毒素。 构效 关系表明与侧边的立体选择性相互作用 链羟基基团的pumiliotoxin生物碱。 当地 麻醉剂抑制了蟾毒的刺激作用 脑内钠流和磷酸肌醇的分解 突触神经体 此外，局部麻醉剂刺激 肌醇掺入磷酸肌醇。 5-取代的- 8-甲基吲哚里西啶显著增强，然后在较高的 浓度抑制放射性结合 全氢组蛋白毒素与烟碱受体通道复合物的结合。 对嗜铬细胞瘤的烟碱受体具有激动剂活性 细胞 其他石斛生物碱，如顺式和 反式-2，5-二取代十氢喹啉，3，5-二取代 吲嗪类、2，5-二取代的吡咯烷类、2，6-二取代的吡咯烷类、 二取代的哌啶和2，6-二取代的-4- 羟基哌啶是结合 过氢组蛋白毒素和具有非竞争性拮抗剂 对嗜铬细胞瘤细胞的烟碱受体的活性。 的 本文研究了树蛙中微量生物碱的生物活性， 作为氮杂三环十二碳烯、脒和氮杂三环十二碳烯， 和三环吲哚生物碱， 肌蛙科的青蛙仍不为人知。 一种脒生物碱是 强效止痛药

Natural products have provided a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over two hundred alkaloids have been identified in extracts from amphibian skins. These include batrachotoxins, which are potent activators of sodium channels, histrionicotoxins. which are noncompetitive blockers of nicotinic receptor channel complexes and of potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity due to inhibitory effects on closing of sodium channels. Pumiliotoxin B acts at a specific site on the sodium channel to increase sodium flux and augments the effects of other sodium channel agents, such as the scorpion toxins and brevetoxins. Structure activity relationships indicate a stereoselective interaction with the side chain hydroxy groups of the pumiliotoxin alkaloids. Local anesthetics inhibit the stimulatory effects of batrachotoxin on both sodium flux and phosphoinositide breakdown in brain synaptoneurosomes. In addition, local anesthetics stimulate incorporation of inositol into phosphoinositides. A 5-substituted- 8-methylindolizidine markedly enhances and then at higher concentrations inhibits binding of radioactive perhydrohistrionicotoxin to the nicotinic receptor-channel complex. It has agonist activity at nicotinic receptors of pheochromocytoma cells. Other dendrobatid alkaloids, such as both the cis- and trans-2,5-disubstituted decahydroquinolines, the 3,5-disubstituted indolizidines, the 2,5-disubstituted pyrrolidines, the 2,6- disubstituted piperidines and a 2,6-disubstituted-4- hydroxypiperidine are potent inhibitors of binding of perhydrohistrionicotoxin and have noncompetitive antagonist activity at nicotinic receptors of pheochromocytoma cells. The biological activity of trace alkaloids from dendrobatid frogs, such as the azatricyclododecenes, the amidines and the homopumiliotoxins, and of the tricyclic indole alkaloids from myobatrachid frogs remain unknown. One amidine alkaloid is a potent analgetic.