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Neurotoxins from Australo-Papuan elapids: A biochemical and pharmacological perspective

Kuruppu, S, Smith, AI, Isbister, GK and Hodgson, WC (2008). Neurotoxins from Australo-Papuan elapids: A biochemical and pharmacological perspective. Critical Reviews in Toxicology,38(1):73-86.

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Title Neurotoxins from Australo-Papuan elapids: A biochemical and pharmacological perspective
Author Kuruppu, S
Smith, AI
Isbister, GK
Hodgson, WC
Journal Name Critical Reviews in Toxicology
Publication Date 2008
Volume Number 38
Issue Number 1
ISSN 1547-6898   (check CDU catalogue open catalogue search in new window)
Start Page 73
End Page 86
Total Pages 14
Place of Publication US
Publisher Informa Healthcare
Field of Research 1115 - Pharmacology and Pharmaceutical Sciences
HERDC Category C1 - Journal Article (DEST)
Abstract Most of the medically important snakes in Papua New Guinea and Australia belong to the family Elapidae and are referred to as “Australo-Papuan” elapids. Neurotoxicity is often a life-threatening symptom of envenoming by these snakes; therefore, much attention has been paid to the isolation and detailed pharmacological and biochemical characterization of the presynaptic (β) and postsynaptic (agr) neurotoxins from these elapid venoms. These studies have highlighted the potential for these toxins to be used as highly potent and selective probes for biomedical research and, perhaps, the potential for their use as lead compounds for the development of pharmaceutical agents. Historically, the potency of neurotoxins/crude venoms has been determined using murine LD50 (lethal dose) assays. However, a different rank order of potency often results when crude venoms/toxins are ranked based on their in vitro pharmacological parameters (e.g., t90 values). The lack of neurotoxicity following envenoming by brown snakes, despite the presence of a potent neurotoxin in their venom, has puzzled clinical toxinologists for years. This paradox also appears to include envenoming by the Stephen's banded snake. Lastly, the in vitro studies examining the effectiveness of antivenoms as well as the potential for alternative compounds to reverse/prevent neurotoxicity are discussed. This review presents for the first time a detailed comparative analysis of the pharmacology and biochemistry of neurotoxins isolated from the Australo-Papuan elapids, placing emphasis on the time taken for onset of action, receptor binding parameters, reversibility, and the methods for determining potency.
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Created: Fri, 16 Apr 2010, 20:36:34 CST by Sarena Wegener