Daly J W
Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, MD 20892-0820, USA.
Braz J Med Biol Res. 1995 Oct;28(10):1033-42.
Amphibian skin has provided a wide range of biologically active alkaloids, many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These include the batrachotoxins, which were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, which were shown to be potent non-competitive blockers and ligands for nicotine receptor channel complexes, the pumiliotoxins and related allo- and homo-pumiliotoxins, which were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, which was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, which was recently identified in feathers and skin of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines, indolizidines, and quinolizidines and tricyclic gephyrotoxins, pyrrolizidine oximes, pseudophrynamines, and coccinellines. These alkaloids also have activity in ion channels. It appears likely that all of the frog skin alkaloids are taken up and sequestered into the skin from the diet, which for such amphibians consists mainly of small arthropods. The pyrrolidines, piperidines, 3,5-disubstituted pyrrolizidines and 3,5-disubstituted indolizidines appear likely to be derived from ants, the coccinellines and related tricyclics from beetles and the pyrrolizidine oximes from millipedes. The origins of the batrachotoxins, histrionicotoxins, pumiliotoxins and epibatidine are of particular interest in view of their remarkable biological activities.
两栖动物的皮肤产生了种类繁多的生物活性生物碱，其中许多具有独特的药理活性和治疗潜力。已鉴定出三百多种生物碱，并阐明了十几种不同类生物碱的结构。这些包括：箭毒蛙毒素，它是钠通道的强效选择性激活剂和配体；蟾蜍毒素，它是烟碱受体通道复合物的强效非竞争性阻滞剂和配体；蟾毒色胺毒素以及相关的别蟾毒色胺毒素和高蟾毒色胺毒素，它们因对钠通道的作用而具有强直性和强心活性；以及埃博霉素，它因对烟碱受体具有选择性激动剂活性而具有强效的抗伤害感受活性。除了最近在一种鸟类的羽毛和皮肤中发现的高箭毒蛙毒素外，这些生物碱仅在两栖动物的皮肤中天然存在。来自两栖动物皮肤的其他生物碱类别包括单环吡咯烷和哌啶、双环十氢喹啉、吡咯里西啶、吲哚里西啶、喹诺里西啶以及三环地棘蛙素、吡咯里西啶肟、假蛙胺和瓢虫素。这些生物碱在离子通道中也具有活性。所有蛙皮生物碱似乎都是从饮食中摄取并储存在皮肤中的，这类两栖动物的饮食主要由小型节肢动物组成。吡咯烷、哌啶、3,5 - 二取代吡咯里西啶和3,5 - 二取代吲哚里西啶似乎来源于蚂蚁，瓢虫素及相关三环化合物来源于甲虫，吡咯里西啶肟来源于千足虫。鉴于其显著的生物活性，箭毒蛙毒素、蟾蜍毒素、蟾毒色胺毒素和埃博霉素的来源尤其令人关注。
