Potent Neurotoxins: Tetrodotoxin, Chiriquitoxin, and Zetekitoxin from Atelopus Frogs in Central America

Abstract

A mixture of the potent neurotoxins tetrodotoxin (TTX) and chiriquitoxin (CHTX) was isolated from the skins of the male and the eggs of the female frog Atelopus chiriquiensis from Costa Rica. Tetrodotoxin was also found in the skin of both populations of Atelopus varius varius and Atelopus varius ambulatorious from Costa Rica. Zetekitoxin(ZTX) was isolated from Atelopus zeteki from Panama. The TTX, CHTX, and ZTX are potent neurotoxins and their toxicities are about the same (ca. 5–11 µg/Kg). The structural studies and biological activities of TTX, CHTX, and ZTX are described.

Keywords: :

• Neurotoxin
• Atelopus frogs
• Tetrodotoxin
• Chiriquitoxin
• Zetekitoxin

Notes

^aR. B. Woodward has speculated that tetrodotoxin may arise in puffer fish “by a variant of the polyacetate scheme with added branching carbon along lines somewhat similar to those used in the construction of sclerotiorin and its relatives” (Woodward, 1964).

^bWe thank P. Siegfried of San Jose, Costa Rica, for collecting these frogs and the Western Zoological Supply of Monrovia, California, for making them available to us.

^cVarian XL‐100 NMR spectrometer operating in the Fourier transform mode. Solutions are prepared from samples lyophilized with D₂O and dissolved in 100 percent D₂O, usually in the presence of about a percent CD₃COOD. We thank the NSF for grant GP 28142 to the Stanford Department of Chemistry for the Varian XL‐100 instrument used in these studies. G. Sullivan made the determinations on this instrument for us.