PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产品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征 活跃性和治疗潜力。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 包括蝙蝠毒素，它是钠的有效激活剂 渠道，剧毒。这些都是非竞争性的拦截者 烟碱受体通道复合体和钾通道，以及 肉毒杆菌毒素，具有强肌和强心活性，原因是 抑制钠通道关闭的作用。短小乳杆菌毒素B 作用于钠通道上的特定位置以增加钠 通量和增强其他钠通道制剂的作用，如 像蝎子毒素和短杆菌毒素一样。结构活性 关系表明与一侧的立体选择性相互作用 褐藻毒素生物碱的链羟基。本地 麻醉药可抑制巴曲霉毒素的兴奋作用 钠离子通量和肌醇磷脂在脑内的分解 突触神经体。此外，局麻药还能刺激 肌醇掺入磷脂酰肌醇。A 5-取代- 8-甲基吲哚利定显著增强，然后在较高的 浓度抑制放射性物质的结合 过氢组氨酸毒素对烟碱受体-通道复合体的作用。 它对嗜铬细胞瘤的烟碱受体具有激动剂活性 细胞。其他树突生物碱，如顺式和顺式 反式-2，5-二取代十氢喹啉，3，5-二取代 2，5-二取代吡咯烷，2，6-取代吡咯烷。 2，6-二取代哌啶和2，6-二取代-4- 羟基哌啶是一种有效的结合抑制剂 过氢组氨酸毒素和有非竞争性拮抗剂 嗜铬细胞瘤细胞烟碱受体活性。这个 树形蛙等微量生物碱的生物活性 作为氮杂环十二烯、酰胺和 高孔毒素和三环吲哚生物碱 肌蛙类仍不为人所知。其中一种烷基生物碱是 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.