PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产品提供了广泛的生物活性 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 通道，组氨酸毒素，这是非竞争性的阻断 烟碱受体通道复合体和钾通道 和具有强肌和强心活性的肉毒杆菌毒素 由于对钠通道关闭的抑制作用。这个 短杆菌毒素B对钠离子通道的影响 激活这些通道，增强神经递质 释放，增强收缩是纹状的和心脏的 肌肉。拟除虫菊酯类毒素和拟除虫菊酯类化合物的刺激作用 其他钠通道药物对心脏功能的影响与 刺激肌醇磷脂周转导致两者 体内钙的动员与蛋白质的活化 角蛋白C对血管内皮细胞钠离子通量的影响 突触神经小体在一定程度上明显增强 多肽毒素，如α-蝎子毒素。各种2，6- 二取代哌啶类药物是一种有效的非竞争性受体阻滞剂 烟碱受体-通道复合体。有一条长边的 链稳定了受体的高亲和力脱敏状态。 局麻药抑制氚巴氏杆菌毒素的结合 通过增强解离来变构模拟或通过 直接竞争。Retpines似乎是真正的竞争对手。 两栖生物碱的新结构类别是 描述并包括2，5-二取代吡咯烷，4-羟基- 2，6-二烷基哌啶，2，5-二取代-反式-2，6-二烷基哌啶 十氢喹啉，一种结构上与 肉毒杆菌毒素--一类生物碱，各种5-取代-8-甲基 吲哚青霉毒素C，氮杂环十二烯， 几个三环胺，以及一个不寻常的亚丙基吡咯-(2，3-b) 吲哚乙酯。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.