PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产物提供了广泛的生物活性， 其中许多药物具有独特的药理作用 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，histrionicotoxins，这是非竞争性块， 烟碱受体通道复合物和钾通道 和具有肌强直和心脏强直活性的短小毒素 这是由于对钠通道关闭的抑制作用。 的 短小毒素B对钠通道的作用导致重复的 激活这些通道，增强神经递质 释放和增强收缩是横纹和心脏 肌肉. pumiliotoxins、拟除虫菊酯和 其他钠通道药物对心功能的影响与 磷酸肌醇周转的刺激导致 动员内部钙并激活蛋白质 激酶C 短小螺旋藻毒素B对小鼠肠钠通量的影响 突触神经体被某些 多肽毒素，如α-蝎毒素。 各种2，6- 二取代的哌啶是有效的非竞争性阻断剂， 烟碱受体通道复合物。 一边长的 链稳定受体的高亲和力脱敏状态。 局部麻醉剂抑制氚化河豚毒素的结合 通过增强解离或通过 直接竞争。 利血平似乎是真正的竞争对手。 两栖类生物碱的新结构类别已被发现， 所描述的化合物包括2，5-二取代的吡咯烷、4-羟基- 2，5-二取代-反式-2，6-二烷基哌啶 十氢喹啉，一种结构上与 pumiliotoxin-一类生物碱，各种5-取代-8-甲基 吲嗪类化合物，羟基嘌呤毒素C，氮杂三环十二碳烯， 几个三环脒，和一个不寻常的异戊二烯基吡咯-（2，3-B） 吲哚酯 这些新生物碱的生物活性是 未知

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 blocks 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. The effects of pumiliotoxin B on sodium channels results in repetitive activations of such channels, enhancement of neurotransmitter release, and potentiation of contraction is striated and cardiac muscle. The stimulatory effects of pumiliotoxins, pyrethroids and other sodium channel agents on cardiac function correlates with stimulation of phosphoinositide turnover leading to both mobilization of internal calcium and to activation of protein kinase C. The effects of pumiliotoxin B on sodium flux in synaptoneurosomes are markedly potentiation by certain polypeptide toxins, such as alpha-scorpion toxin. A variety of 2,6- disubstituted piperidines are potent noncompetitive blockers of the nicotinic receptor-channel complex. Those with one long side chain stabilize high affinity desensitized states of the receptor. Local anesthetics inhibit binding of a tritiated batrochotoxin analog either allosterically by enhancing dissociation or through direct competition. Reserpines appear to be true competitors. New structural classes of amphibian alkaloids have been delineated and include 2,5-disubstituted pyrrolidines, a 4-hydroxy- 2, 6-dialkylpiperidine, 2,5-disubstituted-trans- decahydroquinolines, a quinolizidine related in structure to the pumiliotoxin-A class of alkaloids, various 5-substituted-8-methyl indolizidines a hydroxypumiliotoxin C, an azatricyclododecene, several tricyclic amidines, and an unusual prenyl pyrrole-(2,3-b) indole ester. The biological activity of these new alkaloids is unknown.