SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.
毒性情報
Treatment · 1 件
While it is not an antidote to batrachotocins, the membrane depolarization can be prevented or reversed by either tetrodotoxin, which is a non-competitive inhibitor, or saxitoxin. These both have effects antagonistic to those of batrachotoxin on sodium flux. Certain anaesthetics may act as receptor antagonists to the action of this alkaloid poison, while other local anaesthetics block its action altogether by acting as competitive antagonists. (L1069)
Interactions · 5 件
Two distinct types of local anesthetics (LAs) have previously been found to block batrachotoxin (BTX)-modified Na+ channels: type 1 LAs such as cocaine and bupivacaine interact preferentially with open channels, whereas type 2 LAs, such as benzocaine and tricaine, with inactivated channels. Herein, we describe our studies of a third type of LA, represented by tetracaine as a dual blocker that binds strongly with closed channels but also binds to a lesser extent with open channels when the membrane is depolarized. Enhanced inactivation of BTX-modified Na+ channels by tetracaine was determined by steady-state inactivation measurement and by the dose-response curve. The 50% inhibitory concentration (IC50) was estimated to be 5.2 microM at -70 mV, where steady-state inactivation was maximal, with a Hill coefficient of 0.98 suggesting that one tetracaine molecule binds with one inactivated channel. Tetracaine also interacted efficiently with Na+ channels when the membrane was depolarized; the IC50 was estimated to be 39.5 microM at +50 mV with a Hill coefficient of 0.94. Unexpectedly, charged tetracaine was found to be the primary active form in the blocking of inactivated channels. In addition, external Na+ ions appeared to antagonize the tetracaine block of inactivated channels. Consistent with these results, N-butyl tetracaine quaternary ammonium, a permanently charged tetracaine derivative, remained a strong inactivation enhancer. Another derivative of tetracaine, 2-(di-methylamino) ethyl benzoate, which lacked a 4-butylamino functional group on the phenyl ring, elicited block that was approximately 100-fold weaker than that of tetracaine. We surmise that 1) the binding site for inactivation enhancers is within the Na+ permeation pathway, 2) external Na+ ions antagonize the block of inactivation enhancers by electrostatic repulsion, 3) the 4-butylamino functional group on the phenyl ring is critical for block and for the enhancement of inactivation, and 4) there are probably overlapping binding sites for both inactivation enhancers and open-channel blockers within the Na+ pore
化学と産業
薬理情報
Mechanism of Action · 6 件
Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarization of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure. Since its discovery, field researchers also reported numbness after their skin came into contact with this toxin. Intrigued by this phenomenon, we determined the effect of batrachotoxin on the voltage-gated sodium channel Nav1.8, which is considered to be a key player in nociception. As a result, we discovered that batrachotoxin profoundly modulates this channel: the inactivation process is severely altered, the voltage-dependence of activation is shifted towards more hyperpolarized potentials resulting in the opening of Nav1.8 at more negative membrane potentials and the ion selectivity is modified.
Batrachotoxin (BTX), from South American frogs of the genus Phyllobates, irreversibly activates voltage-gated sodium channels. Previous work demonstrated that a phenylalanine residue approximately halfway through pore-lining transmembrane segment IVS6 is a critical determinant of channel sensitivity to BTX. In this study, we introduced a series of mutations at this site in the Na(v)1.3 sodium channel, expressed wild-type and mutant channels in Xenopus laevis oocytes, and examined their sensitivity to BTX using voltage clamp recording. We found that substitution of either alanine or isoleucine strongly reduced channel sensitivity to toxin, whereas cysteine, tyrosine, or tryptophan decreased toxin action only modestly. These data suggest an electrostatic ligand-receptor interaction at this site, possibly involving a charged tertiary amine on BTX. We then used a mutant channel (mutant F1710C) with intermediate toxin sensitivity to examine the properties of the toxin-receptor reaction in more detail. In contrast to wild-type channels, which bind BTX almost irreversibly, toxin dissociation from mutant channels was rapid, but only when the channels were open, not when they were closed. These data suggest the closed activation gate trapped bound toxin. Although BTX dissociation required channel activation, it was, paradoxically, slowed by strong membrane depolarization, suggesting additional state-dependent and/or electrostatic influences on the toxin binding reaction. We propose that BTX moves to and from its receptor through the cytoplasmic end of the open ion-conducting pore, in a manner similar to that of quaternary local anesthetics like QX314.
The binding site for batrachotoxin, a lipid-soluble neurotoxin acting at Na+ channel receptor site 2, was localized using a photoreactive radiolabeled batrachotoxin derivative to covalently label purified and reconstituted rat brain Na+ channels. In the presence of the brevetoxin 1 from Ptychodiscus brevis and the pyrethroid RU51049, positive allosteric enhancers of batrachotoxin binding, a protein with an apparent molecular mass of 240 kDa corresponding to the Na+ channel alpha subunit was specifically covalently labeled. The region of the alpha subunit specifically photolabeled by the photoreactive batrachotoxin derivative was identified by antibody mapping of proteolytic fragments. Even after extensive trypsinization, and anti-peptide antibody recognizing an amino acid sequence adjacent to Na+ channel transmembrane segment IS6 was able to immunoprecipitate up to 70% of the labeled peptides. Analysis of a more complete digestion with trypsin or V8 protease indicated that the batrachotoxin receptor site is formed in part by a portion of domain I. The identification of a specifically immunoprecipitated photolabeled 7.3-kDa peptide containing transmembrane segment S6 from domain I restricted the site of labeling to residues Asn-388 to Glu-429 if V8 protease digestion was complete or Leu-380 to Glu-429 if digestion was incomplete. These results implicate the S6 transmembrane region of domain I of the Na+ channel alpha subunit as an important component of the batrachotoxin receptor site.
((1S)-1-((1R,5R,6S,9R,11S,12R,14R)-9,12-dihydroxy-6,16-dimethyl-10,19-dioxa-16-azahexacyclo(12.5.3.15,9.01,14.02,11.06,11)tricosa-2,21-dien-22-yl)ethyl) 2,4-dimethyl-1H-pyrrole-3-carboxylate1-(9,12-dihydroxy-6,16-dimethyl-10,19-dioxa-16-azahexacyclo(12.5.3.15,9.01,14.02,11.06,11)tricosa-2,21-dien-22-yl)ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate1-{9,12-dihydroxy-6,16-dimethyl-10,19-dioxa-16-azahexacyclo[12.5.3.15,9.01,14.02,11.06,11]tricosa-2,21-dien-22-yl}ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylateRefChem:116663DTXCID901323802Betrachotoxinin A, 20-alpha-(2,4-dimethyl-1H-pyrrole-3-carboxylate) (9CI)BTXGTPL2619
データベース識別子
CAS
23509-16-2
PubChem CID
6324647
DTXSID
DTXSID50893767
UNII
TSG6XHX09R
Nikkaji
J54.476K
化学的特性Noncrystal.
PURPOSE: To investigate the response to general anesthetics of different sodium-channel subtypes, we examined the effects of pentobarbital, a close thiopental analogue, on single sodium channels from human skeletal muscle and compared them to existing data from human brain and human ventricular muscle channels. METHODS: Sodium channels from a preparation of human skeletal muscle were incorporated into planar lipid bilayers, and the steady-state behavior of single sodium channels and their response to pentobarbital was examined in the presence of batrachotoxin, a sodium-channel activator. Single-channel currents were recorded before and after the addition of pentobarbital (0.34-1.34 mM). RESULTS: In symmetrical 500 mM NaCl, human skeletal muscle sodium channels had an averaged single-channel conductance of 21.0 +/- 0.6 pS, and the channel fractional open time was 0.96 +/- 0.04. The activation midpoint potential was -96.2 +/- 1.6 mV. Extracellular tetrodotoxin blocked the channel with a half-maximal concentration (k1/2) of 60 nM at 0 mV. Pentobarbital reduced the time-averaged conductance of single skeletal muscle sodium channels in a concentration-dependent manner (inhibitory concentration 50% [IC50] = 0.66 mM). The steady-state activation was shifted to more hyperpolarized potentials (-16.7 mV at 0.67 mM pentobarbital). CONCLUSION: In the planar lipid bilayer system, skeletal muscle sodium channels have some electrophysiological properties that are significantly different compared with those of sodium channels from cardiac or from central nervous tissue. In contrast to the control data, these different human sodium channel subtypes showed the same qualitative and quantitative response to the general anesthetic pentobarbital. The implication of these effects for overall anesthesia will depend on the role the individual channels play within their neuronal networks, but suppression of both central nervous system and peripheral sodium channels may add to general anesthetic effects
We have investigated the action of procainamide on batrachotoxin (BTX)-activated sodium channels from bovine heart and rat skeletal muscle. When applied to the intracellular side, procainamide induced rapid, open-channel block. We estimated rate constants using amplitude distribution analysis. Membrane depolarization increased the blocking rate and slowed unblock. The rate constants were similar in both magnitude and voltage dependence for cardiac and skeletal muscle channels. Qualitatively, this block resembled the fast open-channel block by lidocaine, but procainamide was about sevenfold less potent. Molecular modeling suggests that the difference in potency between procainamide and lidocaine might arise from the relative orientation of their aromatic rings, or from differences in the structure of the aryl-amine link. For the cardiac channels, procainamide reduced the frequency of transitions to a long-lived closed state which shows features characteristic of inactivation. Mean durations of kinetically identified closed states were not affected. The degree of fast block and of inhibition of the slow closures were correlated. Internally applied QX-314, a lidocaine derivative and also a fast blocker, produced a similar effect. Thus, drug binding to the fast blocking site appears to inhibit inactivation in BTX-activated cardiac channels.
The purpose of the present study was to examine the characteristics of Na+ channel modification by batrachotoxin (BTX) in cardiac cells, including changes in channel gating and kinetics as well as susceptibility to block by local anesthetic agents. We used the whole cell configuration of the patch clamp technique to measure Na+ current in guinea pig myocytes. Extracellular Na+ concentration and temperature were lowered (5-10 mM, 17 degrees C) in order to maintain good voltage control. Our results demonstrated that 1) BTX modifies cardiac INa, causing a substantial steady-state (noninactivating) component of INa, 2) modification of cardiac Na+ channels by BTX shifts activation to more negative potentials and reduces both maximal gNa and selectivity for Na+; 3) binding of BTX to its receptor in the cardiac Na+ channel reduces the affinity of local anesthetics for their binding site; and 4) BTX-modified channels show use-dependent block by local anesthetics. The reduced blocking potency of local anesthetics for BTX-modified Na+ channels probably results from an allosteric interaction between BTX and local anesthetics for their respective binding sites in the Na+ channel. Our observations that use-dependent block by local anesthetics persists in BTX-modified Na+ channels suggest that this form of extra block can occur in the virtual absence of the inactivated state. Thus, the development of use-dependent block appears to rely primarily on local anesthetic binding to activated Na+ channels under these conditions.
For more Interactions (Complete) data for Batrachotoxin (6 total), please visit the HSDB record page.
Health EffectsBatrachotoxins affect the peripheral nervous system and heart muscles. (L1069)
Exposure Routes · 2 件
Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarisation of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure. Field researchers have reported numbness after their skin came into contact with this toxin.
Injestion or inhalation (smoking). L1810
Toxicity Summary · 3 件
IDENTIFICATION AND USE: Batrachotoxins are neurotoxic steroidal alkaloids first isolated from a Colombian poison-dart frog and later found in certain passerine birds of New Guinea. Neither vertebrate group is thought to produce the toxins de novo, but instead they likely sequester them from dietary sources. HUMAN STUDIES: Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarization of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure. Since its discovery, field researchers also reported numbness after their skin came into contact with this toxin. ANIMAL STUDIES: Levels of batrachotoxin tend to be reduced when P. terribilis is maintained in captivity, but even after being confined for up to 6 years, these frogs were still at least five times more toxic than other Phyllobates species used by natives for poisoning blowgun darts. Batrachotoxin was not detectable in F1 progeny reared to maturity in captivity. Nerve and muscle preparations from wild-caught frogs and from the nontoxic F1 frogs were both insensitive to batrachotoxin. The regulatory site controlling sodium-channel activation and permeability appears to have been minimally altered to prevent interaction with batrachotoxin, but is still sensitive to other sodium conductance activators (veratridine, grayanotoxin) to which the frogs are not exposed naturally.
Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarisation of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure.
Batrachotoxins act on sodium channels by modifying both their ion selectivity and voltage sensitivity. By increasing the permeability of the cell membrane, the cell is depolarized by the influx of sodium. Sodium channels become persistently active at the resting membrane potential and nerve signal transmission to the muscles is blocked. Batrachotoxin also induces a massive release of acetylcholine in nerves and muscles and destroys of synaptic vesicles. (L1069)
Ecotoxicity Excerpts · 1 件
/AQUATIC SPECIES/ A radiosodium flux assay was employed to characterize the pharmacological properties of trout brain voltage-sensitive sodium channels and to define the response of those channels to the synthetic pyrethroid insecticide deltamethrin. The uptake of 22Na+ into trout brain synaptoneurosomes was measured in the presence of a number of sodium channel-directed ligands. The sodium channel activators aconitine, veratridine, and batrachotoxin stimulated 22Na+ uptake into trout brain synaptoneurosomes in a dose-dependent manner. Batrachotoxin was the most efficacious and potent activator having a maximal sodium uptake at saturating concentrations (Emax) of 62 nmol/mg protein and a concentration producing a half maximal response (K05) of 35 uM. ... Deltamethrin also caused a three-fold shift in the potency of batrachotoxin with no effect on Emax. ...
Signs and SymptomsBatrachotoxins interfere with heart conduction, causing arrhythmias, extrasystoles, ventricular fibrillation and other changes which lead to cardiac arrest. (L1069)
Natural Pollution SourcesBatrachotoxin is the active principal steroidal alkaloid isolated from poison-dart (poison-arrow) frogs of the genus Phyllobates.
Human Toxicity Excerpts · 1 件
/SIGNS AND SYMPTOMS/ Batrachotoxin is a potent modulator of voltage-gated sodium channels, leading to irreversible depolarization of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure. Since its discovery, field researchers also reported numbness after their skin came into contact with this toxin.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Non-Human Toxicity Excerpts · 5 件
/ALTERNATIVE and IN VITRO TESTS/ We have studied the effects of batrachotoxin (BTX) on sodium channels in hybrid mouse neuroblastoma cells NG108-15 by using the suction pipet voltage clamp method. BTX-modified sodium channels activate with first-order kinetics and, over most of the potential range, activate more slowly than normal sodium channels. The peak conductance-voltage curve and the time constant of activation-versus-voltage curve for BTX-modified sodium channels are shifted about 50 mV in the hyperpolarizing direction compared to the corresponding curves for normal sodium channels. There is no change in the slope of the conductance-voltage curve. These results suggest that BTX slows down one of the steps leading to channel opening, which consequently becomes rate-limiting. In addition, BTX eliminates both fast and slow inactivation.
/ALTERNATIVE and IN VITRO TESTS/ OBJECTIVES: To investigate the capacity of voltage-gated Na(+) channel activators such as batrachotoxin, aconitine, veratridine, Ts1 (formerly Tityus gamma-toxin), and brevetoxin-3 to induce relaxation of rabbit isolated corpus cavernosum (RbCC) and the pharmacologic mechanisms underlying this phenomenon. The voltage-gated Na(+) channels of the corpus cavernosum are essential for erectile function. A number of biologic toxins exert their effects by modifying the properties of these channels. METHODS: Male New Zealand white rabbits were anesthetized with pentobarbital sodium. Strips of RbCC were transferred to 10-mL organ baths containing oxygenated and warmed Krebs solution. The RbCC strips were connected to force-displacement transducers, and changes in isometric force were recorded using a PowerLab 400 data acquisition system. Corporeal smooth muscle was precontracted submaximally with phenylephrine (10 micromol/L). RESULTS: The binding site-2 (batrachotoxin, aconitine, and veratridine) and binding site-5 (brevetoxin-3) voltage-gated Na(+) channel activators caused slow-onset RbCC relaxations, and the binding site-4 activator Ts1 produced transitory relaxations followed by a return to baseline. The Na(+)channel blockers tetrodotoxin and saxitoxin (0.1 micromol/L each) abolished the relaxations induced by these agonists. Similarly, the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester (100 micromol/L) markedly reduced the relaxations and l-arginine (1 mmol/L) restored the relaxations. The soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxidiazolo[4,3-alpha] quinoxalin-1-one (10 micromol/L) reduced the relaxations, and the phosphodiesterase type 5 inhibitor sildenafil (100 nmol/L) significantly potentiated the relaxations by all activators. CONCLUSIONS: Our results indicate that the relaxations evoked by selective activators of voltage-gated Na(+) channels are mediated by the release of nitric oxide from nitrergic nerves and the activation of the nitric oxide-cyclic guanosine monophosphate pathway in the smooth muscle cells of erectile tissue.
/ALTERNATIVE and IN VITRO TESTS/ The effects of batrachotoxin (BTX) on cloned alpha-subunit Na+ channels were examined in CHO-K1 cells (a chinese hamster ovary cell line) transfected with rat brain NaIIA cDNA. Under whole-cell patch clamp conditions, BTX shifted the voltage dependence of the activation process by about 45 mV towards the hyperpolarizing direction and eliminated the inactivating phase of Na+ currents. Repetitive depolarizations greatly facilitated the binding of BTX with NaIIA channels while the membrane was held at -100 mV. In chloramine-T-pretreated cells, the association rate of BTX binding with the NaIIA channel was 6.5-fold faster than that in untreated cells. The estimated association rate constant for BTX binding with the open form of NaIIA channel was 1.11 x 10(6) mol-1.s-1 at room temperature. BTX-modified NaIIA channels were blocked by tetrodotoxin (TTX) in a complicated manner. First, the TTX binding to the closed state of BTX-modified NaIIA channels was not voltage dependent. The KD value of TTX was measured at 8.9 nM, which was similar to that of unmodified channels (KD = 14.2 nM). Second, the block of the open state of BTX-modified NaIIA channels by TTX was voltage dependent; depolarization reduced the potency of TTX block between -20 mV to +50 mV. Below -30 mV, the TTX affinity began to level off, probably because of the increased presence of the closed state. Unexpectedly, steady-state inactivation of BTX-modified NaIIA channels was minimal as measured by the two-pulse protocol, a phenomenon distinctly different from that found in GH3 cells
/ALTERNATIVE and IN VITRO TESTS/ The mode of action of batrachotoxin (BTX) in isolated papillary muscles of the guinea-pig heart was investigated using conventional methods for mechanical and electrophysiological measurements. The toxic effect of BTX was due to a slowing of the repolarization of the action potential at negative values of membrane potential which initiated a secondary regenerative depolarization associated with an extrasystole. At low concentrations (0.75- 60 nM) the prolonging effect on the action potential appeared only after a series of action potentials had been elicited. For a given effect (increase of action potential duration or production of an extrasystole) the product of BTX concentration and number of preceding action potentials in the presence of BTX was approximately constant. The effect on the action potential developed at a progressively increasing rate during repetitive stimulation. On the assumption of a non-linear relation between the degree of BTX receptor occupation and the effect on action potential duration, the effect of BTX is interpreted to be the consequence of an activity-dependent, irreversible one-to-one binding reaction of BTX with sarcolemmal receptors. Removal of BTX during continued stimulation or interruption of stimulation during continued exposure to BTX caused a gradual disappearance of the effect on the action potential; a residual effect was still present after several hours of washing or rest. These findings indicate a time-dependent very slow dissociation of BTX. Tetrodotoxin (TTX) antagonized the effect of BTX indicating the involvement of fast Na channels. Even when the maximum rate of rise of the action potential was markedly suppressed by TTX, a high concentration of BTX was capable to prolong the action potential and to induce secondary depolarizations. A low fractional occupation of BTX receptors apparently suffices for the production of extrasystoles. The transient hyperpolarization of the resting membrane potential present after prolonged stimulation at 1.0 Hz was significantly increased by BTX suggestive of increased Na pumping. Depolarization to-50 mV by addition of KCl apparently prevented the binding reaction of BTX. It is tentatively suggested that the activity of the fast Na channels (rather than the activity of the slow channels, depolarization, or the mechanical activity) is responsible for the binding of BTX to its receptors. Concomitantly with its effect on the action potential BTX produced a positive inotropic effect by increasing the rate of force development and prolonged the relaxation time. These effects persisted in preparations from reserpine-pretreated animals, but were absent in the presence of TTX. An increased [Na]i, secondary to a prolonged Na permeability during the action potential, and followed by increased Na/Ca exchange, could explain the positive inotropic effect. The first contraction elicited after incubation of a resting muscle with high concentrations of BTX (0.6-1.2 uM) was increased in amplitude and rate of rise. This inotropic effect was absent in muscles from reserpine-pretreated animals. The nerve-depolarizing effect of BTX, causing a release of noradrenaline from adrenergic nerve endings within the muscle, is thought responsible for this effect.
For more Non-Human Toxicity Excerpts (Complete) data for Batrachotoxin (8 total), please visit the HSDB record page.
Antidote and Emergency Treatment · 3 件
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Etiological Agents/
/SRP:/ Basic Treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . /Etiological Agents/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious or is in severe respiratory distress. Monitor cardiac rhythm and treat arrhythmias if necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Proparacaine hydrochloride should be used to assist eye irrigation ... . /Etiological Agents/
安全データ
ridadr
3172
毒性
LD50 s.c. in mice: 2 mg/kg (Tokuyama)
hazard_class
6.1(b)
packing_group
III
有毒物質データの
23509-16-2(Hazardous Substances Data)
The steroidal neurotoxin (-)-batrachotoxin functions as a potent agonist of voltage-gated sodium ion channels (NaVs). Here we report concise asymmetric syntheses of the natural (-) and non-natural (+) antipodes of batrachotoxin, as well both enantiomers of a C-20 benzoate-modified derivative. Electrophysiological characterization of these molecules against NaV subtypes establishes the non-natural toxin enantiomer as a reversible antagonist of channel function, markedly different in activity from (-)-batrachotoxin. Protein mutagenesis experiments implicate a shared binding side for the enantiomers in the inner pore cavity of NaV. These findings motivate and enable subsequent studies aimed at revealing how small molecules that target the channel inner pore modulate NaV dynamics.
Batrachotoxins (BTX): Neurotoxin, activates sodium ion channels, digitalis (digitoxin)-like cardiotoxin, causes fibrillation and cardiac arrest. /from table/
Some birds sequester batrachotoxin (BTX) from their food without poisoning themselves. Birds impervious to BTX have amino acid substitutions in the toxin-binding site of the voltage-gated sodium channel Nav1.4, whose function is essential for proper contraction and relaxation of vertebrate muscles. Poison dart frogs that also co-opted BTX in their lethal mantles were found to harbour similar toxin insensitivity substitutions in their Nav1.4 channels.
用途と製造
Uses · 4 件
Biochemical tool for study of Na+ channels.
Batrachotoxins are neurotoxic steroidal alkaloids that were first isolated from a Colombian poison-dart frog and later found in certain passerine birds of New Guinea. Neither vertebrate group is thought to produce the toxins de novo, and the toxins are likely sequestered from dietary sources. The authors of this publication describe the presence of high levels of batrachotoxins in a little-studied group of small beetles, genus Choresine (family Melyridae), and suggest they might provide a toxin source for the New Guinea birds. Stomach content analyses of Pitohui birds revealed Choresine beetles in the diet, as well as numerous other small beetles and arthropods, and the authors noted that the family Melyridae is cosmopolitan, and that relatives in Colombian rain forests of South America could be the source of the batrachotoxins found in the highly toxic Phyllobates frogs of that region.
Amphibian skin contains several structural classes of alkaloids. These include batrachotoxins, histrionicotoxins, gephyrotoxins, decahydroquinolines, pumiliotoxins and homopumiliotoxins, epibatidine, and samandarines. Some of these alkaloids are derived from the amphibians' diet. Examples include pyrrolizidine and indolizidine alkaloids from ants, tricyclic coccinellines from beetles, and pyrrolizidine oximes, likely sourced from millipedes. However, the origins of other alkaloids, such as batrachotoxins, decahydroquinolines, histrionicotoxins, pumiliotoxins, and epibatidine, are unknown. These alkaloids may be synthesized by the amphibians themselves, produced by symbiotic microorganisms, or possibly obtained from unknown dietary sources.
Batrachotoxins are found in poison dart frogs (genus Dendrobates and Phyllobates), Melyridae beetles, and certain birds (genus Pitohui and Ifrita). (L1069)
Methods of Manufacturing · 2 件
The active principle steroidal alkaloid isolated from poison-dart (poison-arrow) frogs of the genus Phyllobates.
Batrachotoxin is a potent neurotoxin produced by the endangered Colombian poison dart frog and is an agonist of voltage-gated sodium ion channels (NaVs). /Authors/ developed a chemical synthesis of this molecule, denoted (-)-BTX, by taking advantage of a tin hydride-mediated radical cyclization to stitch together the polycyclic framework. Using an analogous route, they also prepared the non-natural mirror image, (+)-BTX. Conversely to the natural product, (+)-BTX antagonized NaVs.
General Manufacturing InformationBatrachotoxins (BTX): Streoidal alkaloids produced by certain Central and Souh American poison dart/arrow frogs (Dendrobates, Phyllobates). /from table/
