Medical Aspects of Chemical Warfare (2008) - The Black Vault

Medical Aspects of Chemical WarfareBatrachotoxinSynthesisBTX (Figure 19-6) is a steroidal alkaloid and theprimary poison of the so-called Colombian PoisonDart Frogs of the genus Phyllobates. These frogs arebrightly colored golden yellow, golden orange, orpale metallic green and they release BTX, as well asfour other steroid toxins, through colorless or milkysecretions from the granular glands in response topredatory threats. It is believed that Phyllobates donot produce BTX, but accumulate the poison by eatingants or other insects in their native habitats thathave obtained BTX from a plant source. The naturalsources of BTX have not been reported; however,frogs raised in captivity do not contain BTX and thusmay be handled without the risk of intoxication, 180,181suggesting that the toxin is the product of anotherorganism. Recent field work has identified BTX intissues of other, unexpected species, including theskin and feathers of some birds from New Guinea,Ifrita kowaldi, and three species of the genus Pitohui.The link between the toxin-bearing birds and frogswas hypothesized to be Melyrid beetles of the genusChoresine. 9,182–185 These beetles contain high concentrationsof BTX and have been discovered in the stomachcontents of captured toxin-bearing bird and frog species(see Figure 19-6).BTX is commonly used by Noanamá Chocó andEmberá Chocó Indians of western Colombia for poisoningblowgun darts used in hunting. The most toxicmember of Phyllobates, (P terribilis, P aurotaenia, andP bicolor), is P terribilis, which can bear a toxic loadup to 1900 µg of toxin. 185 Phyllobates generally containapproximately 50 µg of toxin. Toxin is extractedby Chocó Indians by roasting captured frogs over afire. 186,187 BTX is harvested from blisters that form onthe frog from the heat of the fire and is weaponizedby touching dart or arrow tips to the toxin. The toxincan be stockpiled by collection and fermentation in astorage container, and toxin stocks prepared in thisway are reported to be potent for up to 1 year. 185BTX is a neurotoxin that affects the voltage-gatedsodium channels in a manner similar to the PbTxdiscussed above. Pathologic effects from BTX intoxicationare due to the depolarization of nerve andmuscle cells, which results from an increased sodiumion permeability of the excitable membrane. 188 BTX islipid soluble, and activity is temperature dependentand pH sensitive. The maximum activity of BTX occursat 37°C 185 and at an alkaline pH. 189BTXs bind sodium channels both in muscle cellsand in neurons, modifying both their ion selectivityand voltage sensitivity. 188 The effect of toxin on thesodium channel is to make it constitutively open,causing the irreversible depolarization of cells. 190However, effects are not observed in experimentswhere sodium ions are absent in intracellular andextracellular compartments. In addition, BTX altersthe ion selectivity of the ion channel by increasing thepermeability of the channel toward larger cations. 189In-vitro muscle preparations treated with BTX haveshown massive acetylcholine release in response todepolarization, as predicted. Ultrastructural changeshave been observed in nerve and muscle preparationsand are due to the massive influx of sodium ions thatproduce osmotic alterations. 191Toxin Exposure, Health Effects, and TreatmentBTX-tipped darts have been used to hunt gameby several Indian groups with very effective results,although few Indian groups, notably the Chocó,have adopted its use in warfare. The Chocó fiercelyresisted the Spanish in the late 16th Century, and itis not unlikely that BTX weapons were employed inwarfare during that period. 185Physical Examination. Few published reports havedescribed the systemic effects of BTX intoxication;however, the Chocó Indians claim that a human shotwith a BTX-poisoned dart could run only a few hundredmeters before dying. 185 In 1825 Captain CharlesStuart Cochrane, a Scottish explorer, described hisencounters with the Chocó during an expeditionaround the lowland tropical rain forests of Colombia.Mechanism of Action and ToxicityFig. 19-6. Structure of batrachotoxin, the poison dart frogpoison.Illustration: Courtesy of Richard Sweeny.632