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.
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Garraffo, H M; Spande, T F; Jones, T H et al. (1999) Ammonia chemical ionization tandem mass spectrometry in structure determination of alkaloids. I. Pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines and an azabicyclo[5.3.0]decane. Rapid Commun Mass Spectrom 13:1553-63 |