A pharmacological examination of venoms from three species of death adder (Acanthophis antarcticus, Acanthophis praelongus and Acanthophis pyrrhus)

The common (A. antarcticus), northern (A. praelongus) and desert (A. pyrrhus) death adders are species belonging to the Acanthophis genus. The present study compared some pharmacological aspects of the venoms of these species and examined the in vitro efficacy of death adder antivenom. Neurotoxicity was determined by the time to produce 90% inhibition (t(90)) of indirect (0.1 Hz, 0.2 ms, supramaximal voltage) twitches in the chick biventer cervicis nerve-muscle (3-10 microg/ml) and mouse phrenic nerve-diaphragm (10 microg/ml) preparations. A. praelongus venom was significantly less neurotoxic than A. antarcticus venom but was not significantly different from A. pyrrhus venom. In the biventer muscle, all three venoms (3-10 microg/ml) abolished responses to exogenous ACh (1 mM) and carbachol (20 microM), but not KCl (40 mM), indicating activity at post-synaptic nicotinic receptors. All venoms (30 microg/ml) failed to produce significant inhibition of direct twitches (0.1 Hz, 2.0 ms, supramaximal voltage) in the chick biventer cervicis nerve-muscle preparation. However, A. praelongus (30 microg/ml) venom initiated a significant direct contracture of muscle, indicative of some myotoxic activity. The prior (10 min) administration of death adder antivenom (1 unit/ml), which is raised against A. antarcticus venom, markedly attenuated the twitch blockade produced by all venoms (10 microg/ml). Administration of antivenom (1.5 units/ml) at t(90) markedly reversed, over a period of 4 h, the inhibition of twitches produced by A. praelongus (3 microg/ml, 72+/-6% recovery) and A. pyrrhus (3 microg/ml, 51+/-9% recovery) but was less effective against A. antarcticus venom (3 microg/ml, 22+/-7% recovery). These results suggest that all three venoms contain postsynaptic neurotoxins. Death adder antivenom displayed differing efficacy against the in vitro neurotoxicity of the three venoms.