Batracotoxina

http://www.ncbi.nlm.nih.gov/pubmed/7476906

http://books.google.com.co/books?id=EUBNE4Y0v9sC&pg=PA225&lpg=PA225&dq=epibatidina&source=bl&ots=z_xQVWKMfT&sig=m6xGbuoLV_Djgz-ZswlDKQ9Pnlw&hl=es-419&sa=X&ei=xebuUtXvBK_isATxnYCoAw&ved=0CFkQ6AEwCA#v=onepage&q=epibatidina&f=true

Epibatidina

Epibatidina

Nombre (IUPAC) sistemático

(1R,2R,4S)-(+)-6-(6-cloro-3-piridil)7-azabiciclo[2.2.1]heptano

Fórmula molecular

C11H13N2Cl

Identificadores

Número CAS

140111-52-01

Propiedades físicas

Masa molar

208,69 g/mol

Punto de fusión

424,5 K (151 °C)

Riesgos

Tóxico

Valores en el SI y en condiciones estándar

(25 °C y 1 atm), salvo que se indique lo contrario.

La Epibatidina es un compuesto heterocíclico extraído de una rana multicolor del Ecuador, la Epipedobates tricolor. Es una alcaloide natural de tipo piridínico con actividad farmacológica. Es una sustancia que posee una actividad analgésica 250 veces más potente que la de la morfina y además no provocaba los efectos secundarios de ésta (adicción). Sin embargo, la epibatidina es demasiado tóxica para ser utilizada como analgésico en los seres humanos.

Epipedobates tricolor

Descubrimiento[editar • editar código]

En la década de los setenta se descubre la rana que contiene la epibatidina, pero no es hasta la década de los ochenta cuando se descubre que entre todas las tóxinas que contienen la rana está la epibatidina. Es en 1992 cuando se da una síntesis de la epibatidina y se analiza su estructura. Lo realiza el grupo de investigación de John Daly.2

Desde su descubrimiento se han diseñado tanto síntesis directas3 como síntesis de análogos4 que evitan la alta toxicidad. Uno de los análogos es la Tebaniciclina (ABT – 594).

HISTRIONICOTOXINA

Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the Dendrobatidae family, notably Oophaga histrionica.[1] It is likely that as with other poison frog alkaloids, histrionicotoxins are not manufactured by the amphibians, but absorbed from insects in their diet and stored in glands in their skin.[2]

Histrionicotoxins are less powerful toxins compared to many of the other alkaloids found in poison frogs; however, they have an unusual chemical structure and a distinct mechanism of action, acting as a potent non-competitive antagonists of nicotinic acetylcholine receptors, binding to a regulatory site on the delta subunit of the ion channel complex.[3][4] They also have some affinity for sodium and potassium channels, although they are much less potent for these targets.[5] The synthesis of histrionicotoxins and various homologues is synthetically challenging and has been the subject of many different attempts.

BATRACHOTOXINS

Batrachotoxins (BTX) are extremely potent cardiotoxic and neurotoxic steroidal alkaloids found in certain species of frogs (poison dart frog), melyrid beetles, and birds (Pitohui, Ifrita kowaldi, Colluricincla megarhyncha). It is the most potent non-peptidal neurotoxin known.[1]

History

It was named by scientists John Daly and Bernhard Witkop, who separated the potent toxic alkaloids fraction and determined chemical properties. Due to the difficulty of handling such a potent toxin and the minuscule amount that could be collected, a comprehensive structure determination involved several sufferings. However, Takashi Tokuyama, who joined to the investigation later, converted one of congener compounds, Batrachotoxinin A, to a crystalline derivative and its unique steroidal structure was solved with x-ray diffraction techniques (1968).[2] When the mass spectrum and NMR spectrum of batrachotoxin and the batrachotoxinin A derivatives were compared, it was realized that the two shared the same steroidal structure and that batrachotoxin was batrachotoxinin A with a single extra pyrrole moiety attached. The structure of batrachotoxin was established in 1969 through chemical recombination of both fragments.[3] Batrachotoxinin A was synthesized by Michio Kurosu, Lawrence R. Marcin, Timothy J. Grinsteiner, and Yoshito Kishi in 1991.[4]

Toxicity

Extrapolating from the LD50 in rats, the lethal dose of this alkaloid in humans is estimated to be 1 to 2 µg/kg. Thus, the lethal dose for a 68 kg (150 pound) person would be approximately 100 micrograms, or equivalent to the weight of two grains of ordinary (fine) table salt (NaCl). Batrachotoxin is thus around fifteen times more potent than curare (another arrow poison used by South American Indians and derived from plants of the genera Strychnos and Curarea), and about ten times more potent than tetrodotoxin, from the puffer fish.

The toxin is released through colourless or milky secretions from glands located on the back and behind the ears of frogs from the genus Phyllobates. When one of these frogs is agitated, feels threatened or is in pain, the toxin is reflexively released through several canals.

As a neurotoxin it affects the nervous system. Neurological function depends on depolarization of nerve and muscle fibres due to increased sodium ion permeability of the excitable cell membrane. Lipid-soluble toxins such as batrachotoxin act directly on sodium ion channels[1] involved in action

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