The
venom of the Australian lowlands copperhead, Austrelaps superbus, produces significant and potentially lethal neurotoxic
paralysis in cases of clinical envenomation. However, little is known about the neurotoxic components within this
venom or
venoms from the related alpine copperhead (Austrelaps ramsayi) or pygmy copperhead (Austrelaps labialis). Using the isolated chick biventer cervicis nerve-muscle preparation, all Austrelaps
venoms were found to exhibit potent and rapid inhibition of nerve-evoked twitch contractions and block of
contractures to
nicotinic agonists, consistent with postsynaptic neurotoxic activity. Following separation by size-exclusion liquid chromatography under non-denaturing conditions, all Austrelaps
venoms were found to also contain a high molecular mass fraction with only weak
phospholipase A(2) (PLA(2)) activity that caused a slow inhibition of twitch contractions, without inhibiting
contractures to
nicotinic agonists. These actions are consistent with the presence of additional snake presynaptic PLA(2)
neurotoxin (SPAN) complexes in all three Austrelaps
venoms. However, there was no evidence of direct muscle damage produced by any Austrelaps
venom or SPAN complex. Monovalent tiger snake
antivenom was effective in neutralising the neurotoxicity of both whole
venom and the SPAN complex. However
antivenom was unable to effectively reverse whole
venom neurotoxicity, or prejunctional SPAN neurotoxicity, once established. Given the strong neurotoxicity of all Austrelaps
venoms, particularly A. ramsayi and A. labialis, effective
bites from these copperhead species should be considered potentially lethal. Furthermore, clinicians need to be aware of possible irreversible presynaptic neurotoxicity following envenomation from all copperhead species and that early
antivenom intervention is important in preventing further development of toxicity.