PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

已经鉴定了200多种生物碱， 青蛙皮的提取物。 其中大多数代表独特的结构， 有助于青蛙对抗捕食者的化学防御。 新结构 两栖类生物碱的种类包括三环色胺单萜， 4-羟基2，6-二烷基哌啶，和非羟基化同系物， 2，5-二烷基吡咯烷、3，8-二烷基吲哚嗪和脒。 的 生物碱显示出一系列药理活性。 甾体 蛙毒素是电压依赖性钠通道的有效激活剂。 放射性蛙毒素类似物与钠相关位点结合 大脑和电沉积中的通道，并提供了一个独特的工具， 机制，变构和直接通过局部麻醉剂和 其它药物拮抗钠通道开放。 螺哌啶 historionicotoxins，三环gephyrotoxins和indolizidine 生物碱是烟碱乙酰胆碱的非竞争性变构阻滞剂 受体通道复合物。 此外，组蛋白毒素与 苯环利定敏感位点的中央钾通道，并影响 二氢吡啶与中央钙通道位点的结合。 Pumiliotoxin B是一种亚烷基-羟基吲哚里西啶， 和肌强直剂，其作用和某些其他心脏 兴奋剂似乎涉及钠通量的激活， 刺激磷脂酰肌醇分解导致钙 蛋白激酶C的动员和活化。 某些疏水双- 和单酚检测作为生物碱的环境污染物 组分是非常有效的肌肉Ca++-ATP酶抑制剂 肌浆网

Over two hundred pharmacologically active alkaloids have been identified in extracts of frog skins. Most of these represent unique structures and serve the frogs in chemical defense against predators. New structural classes of amphibian alkaloids include tricyclic tryptamine monoterpenes, 4-hydroxy 2,6-dialkylpiperidines, and non-hydroxylated congeners, 2,5-dialkylpyrrolidines, 3,8 dialkylindolizidines and amidines. The alkaloids exhibit a range of pharmacological activities. The steroidal batrachotoxins are potent activators of voltage-dependent sodium channels. A radioactive batrachotoxin analog binds to sites associated with sodium channels in brain and electroplax and provides a unique tool for probing mechanisms, both allosteric and direct through which local anesthetics and other drugs antagonize sodium channel opening. The spiropiperidine historionicotoxins, the tricyclic gephyrotoxins and the indolizidine alkaloids are noncompetitive allosteric blockers of nicotinic acetylcholine receptor channel complexes. In addition, histrionicotoxins interact with phencyclidine-sensitive sites on central potassium channels, and affect binding of dihydropyridines to sites on central calcium channels. Pumiliotoxin B, an alkylidene-hydroxyindolizidine, is a potent cardiotionic and myotonic agent, whose action and that of certain other cardiac stimulants appears to involve activation of sodium flux and a resultant stimulation of phosphatidyl inositol breakdown leading to both calcium mobilization and activation of protein kinase C. Certain hydrophobic bis- and monophenols detected as environmental contaminants of alkaloid fractions are very potent inhibitors of Ca++-ATPase from muscle sarcoplasmic reticulum.