Frequency-dependent neuromuscular blockade by textilotoxin in vivo

Lloyd, Davina; Nicholson, Graham M.; Spence, Ian; Connor, Mark; Tyler, Margaret I.; Howden, M.E.H.

doi:10.1016/0041-0101(91)90199-2

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…Pre mixing experiments under these conditions showed that sufficient antibody was present to fully neutralize this component. These irreversible features are highly indicative of the pre‐synaptic phospholipase neurotoxin, textilotoxin ( Simpson et al ., 1993 ; Lloyd et al ., 1991 ; Su et al ., 1983 ).…”

Section: Discussionmentioning

confidence: 99%

“…Its exact mechanism of action remains unknown, but is dependant on both temperature and the frequency of nerve stimulation. In addition, textilotoxin is said to be unaffected by antitoxin treatment once the initial binding phase is completed ( Lloyd et al ., 1991 ; Simpson et al ., 1993 ; Hamilton et al ., 1980 ; Cull‐Candy et al ., 1976 ).…”

Section: Introductionmentioning

confidence: 99%

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The effects of specific antibody fragments on the ‘irreversible’ neurotoxicity induced by Brown snake (Pseudonaja) venom

Jones

Lee

Landon

1999

British J Pharmacology

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1 Brown snake (Pseudonaja) venom has been reported to produce`irreversible' post synaptic neurotoxicity (Harris & Maltin, 1981;Barnett et al., 1980). 2 A murine phrenic nerve/diaphragm preparation was used to study the neurotoxic e ects of this venom and pre-and post-synaptic components were distinguished by varying the temperature and frequency of nerve stimulation. There were no myotoxic e ects and the neurotoxicity proved irreversible by washing alone.3 The e ects of a new Fab based ovine antivenom have been investigated and proved able to produce a complete, rapid (51 h) reversal of the neurotoxicity induced by Brown snake venom. A reversal was also possible when the antivenom addition was delayed for a further 60 min. 4 We believe that this is the ®rst time such a reversal has been shown.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effects of specific antibody fragments on the ‘irreversible’ neurotoxicity induced by Brown snake (Pseudonaja) venom

Jones

Lee

Landon

1999

British J Pharmacology

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“…In addition neuromuscular blockade (q) was also determined from the % change in twitch contraction amplitude (t 1 ) every 10 min. Values represent the mean ± SEM after the addition of 20 µg/ml β-bungarotoxin (n = 4), 10 µg/ml textilotoxin (n = 4), 10 µg/ml taipoxin (n = 4), 10 µg/ml notexin (n = 5) Kamenskaya and Thesleff 1974;Chang and Lee 1977;Lloyd et al 1991). Also there was a greater extent of fade in the tetanic fade experiments compared to that seen in the train-of-four fade experiments.…”

Section: Tetanic Fadementioning

confidence: 90%

Presynaptic snake β-neurotoxins produce tetanic fade and endplate potential run-down during neuromuscular blockade in mouse diaphragm

Wilson

Nicholson

1997

Naunyn-Schmiedeberg's Arch Pharmacol

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The present study investigated the ability of a number of presynaptic snake neurotoxins (snake beta-neurotoxins) to produce nerve-evoked train-of-four fade, tetanic fade and endplate potential run-down during the development of neuromuscular blockade in the isolated mouse phrenic-hemidiaphragm nerve-muscle preparation. All the snake beta-neurotoxins tested, with the exception of notexin, produced train-of-four and tetanic fade of nerve-evoked isometric muscle contractions. Train-of-four fade was not present during the initial depressant or facilitatory phases of muscle tension produced by the snake beta-neurotoxins but developed progressively during the final depressant phase that precedes complete neuromuscular blockade. The 'non-neurotoxic' bovine pancreatic phospholipase A2 and the 'low-toxicity' phospholipase A2 from Naja naja atra venom failed to elicit train-of-four fade, indicating that the phospholipase activity of the snake beta-neurotoxins is not responsible for the development of fade. Intracellular recording of endplate potentials (EPPs) elicited by nerve-evoked trains of stimuli showed a progressive run-down in EPP amplitude during the train following incubation with all snake beta-neurotoxins except notexin. Again this run-down in EPP amplitude was confined to the final depressant phase of snake beta-neurotoxin action. However when EPP amplitude fell to near uniquantal levels (< 3 mV) the extent of toxin induced-fade was reduced. Unlike postjunctional snake alpha-neurotoxins, prejunctional snake beta-neurotoxins interfere with acetylcholine release at the neuromuscular junction during the development of neuromuscular blockade. This study provides further support for the hypothesis that fade in twitch and tetanic muscle tension is due to an underlying rundown in EPP amplitude resulting from a prejunctional alteration of transmitter release rather than a use-dependent block of postjunctional nicotinic receptors.

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“…Produces an increase in heart rate prior to death but no changes in the shape of the ECG (Lloyd et al, 1991) Phospholipase A 2 inhibitors have been isolated from the serum of elapid snakes (Hains and Broady, 2000) and other snakes (Okumura et al, 1999) Toxin (Rogowski et al, 1994) DTT delays death in mice (Silva et al, 1994). A non-toxic protein fraction has been isolated from venom, which, when used to immunize mice, provides protection to 10 LD 50 of the toxic fraction (Moreira-Ferreira et al, 1998) Tricothecene mycotoxins (T-2)* These are the most potent small-molecule inhibitors of protein synthesis and also inhibit DNA and RNA synthesis (Ueno et al, 1973;Rosenstein and LeFarge-Frayssinet, 1983).…”

Section: Clostridium Perfringensmentioning

confidence: 97%

Therapy and prophylaxis of inhaled biological toxins

Paddle¹

2003

J of Applied Toxicology

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This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors. Thus, methods involving molecular modelling are limited by the extent to which the cellular receptor sites and mode of action and structure of a toxin need to be known. There is also our general lack of knowledge of what effect individual toxins will have when inhaled into the lungs - whether and to what extent the action will be cell specific and cytotoxic or rather an acute inflammatory response requiring the use of immunomodulators. Possible sources of specific high-affinity toxin antagonists being investigated include monoclonal antibodies, selected oligonucleotides (aptamers) and derivatized dendritic polymers (dendrimers). The initial selection of suitable agents of these kinds can be made using cytotoxicity assays involving cultured normal human lung cells and a range of suitable indicators. The possibility that a mixture of selected antibody, aptamer or dendrimer-based materials for one or more toxins could be delivered simultaneously as injections or as inhaled aerosol sprays should be investigated.

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Frequency-dependent neuromuscular blockade by textilotoxin in vivo

Cited by 5 publications

References 6 publications

The effects of specific antibody fragments on the ‘irreversible’ neurotoxicity induced by Brown snake (Pseudonaja) venom

The effects of specific antibody fragments on the ‘irreversible’ neurotoxicity induced by Brown snake (Pseudonaja) venom

Presynaptic snake β-neurotoxins produce tetanic fade and endplate potential run-down during neuromuscular blockade in mouse diaphragm

Therapy and prophylaxis of inhaled biological toxins

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