PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产品提供了广泛的生物活性物质， 其中许多化合物具有独特的药理活性和 治疗潜力。已经有400多种生物碱 从两栖动物皮肤的提取物中鉴定出来。这些措施包括 蝙蝠毒素是钠通道的强效激活剂， 组氨酸毒素，是尼古丁的非竞争性阻滞剂 受体通道复合体和钾通道，短链毒素， 由于对钠的影响而具有强肌和强心活性 通道，和依巴替丁，一种非常有效和选择性的尼古丁 具有显著抗伤害感受活性的激动剂。进一步的生物碱 包括2，5-二取代十氢喹啉、3，5-二取代 吡咯里齐啶，3，5-二取代中氮杂环，5，8-二取代 吲哚里西定、1，4-二取代和4，6-二取代喹啉， Pumiliotoxin-homopumiliotoxin-allopumiliotoxin类和一个 三环生物碱的种类，包括吡咯里西定肟， 假性苯丙胺、环戊喹啉和球孢菌素。多数 其中的生物碱已经从 新热带树突蛙类。腐霉毒素也存在于一个属中。 产于南美洲一个属的澳大利亚肌蛙类 中华蟾蜍和马达加斯加的一种袋蛙。它 似乎所有的蛙皮生物碱都有饮食来源，正在被摄取 并原封不动地隔离到皮肤腺中。蚂蚁、甲虫和 千足虫似乎是某些蛙皮生物碱的来源。 现在已经在蚂蚁身上发现了十氢喹啉类药物。的起源 巴曲霉毒素、组氨酸毒素、短杆藻毒素和表巴替丁 在青蛙皮肤中发现的这种物质仍然是一个谜。结构现在已经被 测定了1，4-二取代喹诺利定，三取代 吲哚利定，一种与球藻碱类有关的新型三环生物碱， 一种二聚十氢喹啉，一组十九碳 青蛙和蚂蚁中的十氢喹啉类化合物和一种含环氧环己烷 别毒杆菌毒素。螺吡咯烷酮肟类，拟苯丙氨酚，a 托烷生物碱系列(潜在的毒鼠碱/烟碱激动剂) 和强效烟碱的甲基异恶唑类似物(表巴西定) 合成了用于生物评价的止痛药表巴替丁。

Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over four 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 potassium channels, pumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, an extremely potent and selective nicotinic agonist with remarkable antinociceptive activity. Further alkaloids include 2,5-disubstituted decahydroquinolines, 3,5-disubstituted pyrrolizidines , 3,5-disubstituted indolizidines, 5,8-disubstituted indolizidines, 1,4-disubstituted and 4,6-disubstituted quinolizidines, the pumiliotoxin-homopumiliotoxin-allopumiliotoxin class, and a variety of tricyclic alkaloids, including pyrrolizidine oximes, pseudophrynamines, cyclopentaquinolizidines and coccinellines. Most of these alkaloids have been detected and characterized from neotropical dendrobatid frogs. Pumiliotoxins also occur in one genus of Australian myobatrachid frogs, in one genus of South American bufonid toads and in one genus of Madagascan mantellid frogs. It appears all frog skin alkaloids have a dietary origin, being taken up and sequestered unchanged into skin glands. Ants, beetles and millipedes appear to be the source of certain frog skin alkaloids. Decahydroquinolines have now been discovered in ants. The origin of the batrachotoxins, histrionicotoxins, pumiliotoxins, and epibatidines found in frog skin remains a mystery. Structures have now been determined for a 1,4-disubstituted quinolizidine, a trisubstituted indolizidine, a novel tricyclic alkaloid related to the coccinellines, a dimeric decahydroquinoline, a set of nineteen-carbon decahydroquinolines from frogs and ants and an oxirane-containing allopumiliotoxin. Spiropyrrolizidine oximes, pseudophrynaminol, a series of tropane alkaloids (potential muscarinic/nicotinic agonists) and a methylisooxazole analog (epiboxidine) of the potent nicotinic analgetic epibatidine have been synthesized for biological evaluation.